Please wait a minute...
Shopping Cart Email List Chinese
Advanced Search Fig/Tab
Frontiers in Biology

ISSN 1674-7984

ISSN 1674-7992(Online)

CN 11-5892/Q

Featured Articles  |  Most Downloaded  |  Most Reading
Online Submission Subscribe to Our RSS Content Feed
Front. Biol.    2016, Vol. 11 Issue (5) : 376-386    https://doi.org/10.1007/s11515-016-1424-0
REVIEW
Phosphodiesterase 4 inhibitors and drugs of abuse: current knowledge and therapeutic opportunities
Christopher M. Olsen1,2(),Qing-Song Liu1,2()
1. Department of Pharmacology and Toxicology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA
2. Neuroscience Research Center, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA
 Download: PDF(290 KB)   HTML
 Export: BibTeX | EndNote | Reference Manager | ProCite | RefWorks
Abstract

BACKGROUND: Long-term exposure to drugs of abuse causes an upregulation of the cAMP-signaling pathway in the nucleus accumbens and other forebrain regions, this common neuroadaptation is thought to underlie aspects of drug tolerance and dependence. Phosphodiesterase 4 (PDE4) is an enzyme that the selective hydrolyzes intracellular cAMP. It is expressed in several brain regions that regulate the reinforcing effects of drugs of abuse.

OBJECTIVE: Here, we review the current knowledge about central nervous system (CNS) distribution of PDE4 isoforms and the effects of systemic and brain-region specific inhibition of PDE4 on behavioral models of drug addiction.

METHODS: A systematic literature search was performed using the Pubmed.

RESULTS: Using behavioral sensitization, conditioned place preference and drug self-administration as behavioral models, a large number of studies have shown that local or systemic administration of PDE4 inhibitors reduce drug intake and/or drug seeking for psychostimulants, alcohol, and opioids in rats or mice.

CONCLUSIONS: Preclinical studies suggest that PDE4 could be a therapeutic target for several classes of substance use disorder. We conclude by identifying opportunities for the development of subtype-selective PDE4 inhibitors that may reduce addiction liability and minimize the side effects that limit the clinical potential of non-selective PDE4 inhibitors. Several PDE4 inhibitors have been clinically approved for other diseases. There is a promising possibility to repurpose these PDE4 inhibitors for the treatment of drug addiction as they are safe and well-tolerated in patients.
Keywords PDE4      PDE4 inhibitors      VTA      nucleus accumbens      drug addiction     
Corresponding Author(s): Christopher M. Olsen,Qing-Song Liu   
Online First Date: 17 October 2016    Issue Date: 04 November 2016
 Cite this article:   
Christopher M. Olsen,Qing-Song Liu. Phosphodiesterase 4 inhibitors and drugs of abuse: current knowledge and therapeutic opportunities[J]. Front. Biol., 2016, 11(5): 376-386.
 URL:  
https://academic.hep.com.cn/fib/EN/10.1007/s11515-016-1424-0
https://academic.hep.com.cn/fib/EN/Y2016/V11/I5/376
Locomotor sensitization
(Pierce and Kalivas, 1997; Robinson and Berridge, 1993,2008)		 Locomotor sensitization is a phenomenon where the locomotor response to a drug (e.g., amphetamine) is increased in animals with a history of repeated drug exposure. Previous studies have observed this increase for up to one year following cessation of drug treatment. The basis for this test is that locomotor sensitization may reflect long-lasting neuroadaptations and behavioral changes following repeated drug exposure, such as increased craving following exposure to drug cues.
Conditioned place preference
(Bardo and Bevins, 2000; Tzschentke, 2007;Olsen et al., 2010;Liu et al., 2014)		 The conditioned place preference (CPP) test is a behavioral test that measures an animal’s preference for a place that is associated with previous exposure to a reward.
CPP protocols are typically divided into three phases: a pre-test, a conditioning phase, and a post-test. In the pre-test, a drug naïve animal is allowed to explore the entire CPP apparatus (typically composed of two or three distinct, but connected chambers). During the conditioning phase, the animal spends time confined to each of the chambers, however one chamber is paired with a reward (e.g., cocaine), while the other chamber is not (e.g. saline). After several of these pairing sessions, the animal undergoes the post-test in which the animal again is allowed to explore the entire CPP apparatus in a drug free state. The conditioned place preference is typically measured in one of two ways: 1) the difference in time spent in the reward paired chamber between the pre-test and post-test or 2) the difference in the post-test time spent in the reward paired chamber and the non-reward paired chamber. These outcome measures are collected while the animal is in a drug-free state.
Intravenous drug self-administration
(Thomsen and Caine, 2005;Olsen and Winder, 2006;Allain et al., 2015; Muelbl et al., 2016)		 Intravenous drug self-administration is a measure of the reinforcing properties of a drug. The basis of this test is that a positive outcome associated with a response will increase the likelihood of the response in the future. Thus, intravenous drug self-administration is a type of operant (instrumental) conditioning that uses intravenous infusion of a drug as the reinforcer.
An animal with a chronic venous catheter is placed into an operant conditioning chamber, where it learns that a response on the “active” manipulanda (e.g., a lever) results in a drug infusion, whereas a response on the “inactive” manipulanda has no consequence. Drug self-administration is considered to be acquired when there is selectivity in responses on the active manipulanda relative to the inactive one. The effects of treatments on drug self-administration are typically measured as a change in drug self-administration relative to previously stabilized intake. This outcome measure is collected while the animal is under the influence of the drug of abuse.
Reinstatement of drug seeking
(Shaham et al., 2003; Conrad et al., 2013; Mantsch et al., 2016)		 Reinstatement of drug seeking is a measure of drug seeking that is evoked by a stimulus. The basis of this test is that drug seeking (either using the CPP or the operant response in a drug self-administration test) is first extinguished by dissociating the connection between the drug and the drug conditioned response through repeated testing without the drug, then reinstated with a stimulus. Stimuli that are commonly used to reinstate drug seeking include drug-associated cues, stress, or a priming dose of the drug itself. These stimuli are known to also elicit craving in human drug users. The outcome measures are active and inactive manipulandum responding or time spent in the drug and nondrug paired sides (depending on if this is a self-administration or CPP test respectively). These measures are collected while the animal is in a drug-free state (unless drug priming is used to reinstate drug seeking).
Two bottle choice test for alcohol drinking
(Rodd et al., 2004; Crabbe, 2014; Lim et al., 2015; Muelbl et al., 2016 ) 		The two bottle choice test is a measure of voluntary alcohol intake and preference. In this test, alcohol is concurrently available with water and food, so alcohol intake is driven by hedonic processes as opposed to metabolic need. Outcome measures are total alcohol intake and preference (% of total fluid intake that is alcohol), and are collected while the subject is under the influence of the drug.
Intracranial self-stimulation
(Carlezon and Chartoff, 2007; Britt et al., 2012; Ikemoto and Bonci, 2014; Negus and Miller, 2014)		 Intracranial self-stimulation measures the reinforcing properties of electrical or optogenetic stimulation of brain reward circuitry. The basis of this test is that direct stimulation of some brain regions (e.g., ventral tegmental area) or specific pathways (e.g., ventral hippocampus to nucleus accumbens) is innately reinforcing. Thus, operant conditioning is performed using stimulation as the primary reinforcer. Data from intracranial self-stimulation experiments are commonly represented as response rates across a series of stimulus intensities (or frequencies), and treatments that enhance brain stimulation reward will produce a left-shift in this intensity-response curve. These outcome measures are collected while the animal is in a drug-free state, unless a treatment is tested for its ability to modulate drug-enhanced brain stimulation reward.
Drug discrimination
(Young, 2009; Stolerman et al., 2011)		 Drug discrimination is a test that measures the discriminative stimulus effects of a drug. Psychoactive drugs produce subjective feelings, which can be used to signal that a specific behavioral response is required to earn a reward. For example, an animal can be trained that after a saline infusion, pressing the left lever in an operant conditioning chamber will deliver a food pellet. However, after a cocaine infusion, only presses on the left lever deliver a food pellet. Test sessions occur in the absence of food reward, and the outcome measure is the percentage of cocaine- or saline-appropriate responses after each treatment.
There are two main types of drug discrimination tests: stimulus antagonism and stimulus generalization. A stimulus antagonism drug discrimination test can be used to measure the ability of a different drug to reduce the discriminative stimulus properties of the comparator drug. For example, pretreatment with flumazenil (an antagonist of the benzodiazepine binding site of the GABA-A receptor) reduces the percentage of diazepam-appropriate responses in rats trained to discriminate diazepam from saline. A stimulus generalization drug discrimination test assesses the ability of a drug to generalize to another comparative drug. For example, treatment with amphetamine will produce cocaine-appropriate responding in animals trained to discriminate cocaine from saline. Data are collected while the animal is under the influence of the drug.
Tab.1  Behavioral tests commonly used in the study of drugs of abuse
Fig.1  Selective PDE4 inhibitors rolipram and Ro 20-1724 blocked I-LTD in VTA dopamine neurons. (A) The presence of cocaine (3 µM; indicated by horizontal bar) during the 10 Hz stimulation (indicated by arrow “↑”) induced I-LTD in VTA dopamine neurons (n = 6). This I-LTD was blocked by PDE4 inhibitors rolipram (1 µM; n = 8; p<0.05 vs. control) and Ro 20-1724 (200 µM; n = 8; p<0.05 vs. control). The PDE4 inhibitors were present throughout the whole-cell recordings. Sample IPSCs before (indicated by “1”) and after (indicated by “2”) the 10 Hz stimulation are shown on the top. (B) The presence of D2 receptor agonist quinpirole (1 µM) during the 10 Hz stimulation induced I-LTD in VTA dopamine neurons (n = 7). This I-LTD was blocked by rolipram (1 µM; n = 8; p<0.05 vs. control) or Ro 20-1724 (200 µM; n = 7; p<0.05 vs. control). Error bars indicate SEM (used with the permission of Neuropsychopharmacology).
1 Alberini C M (2009). Transcription factors in long-term memory and synaptic plasticity. Physiol Rev, 89(1): 121–145
https://doi.org/10.1152/physrev.00017.2008 pmid: 19126756
2 Allain F, Minogianis E A, Roberts D C, Samaha A N (2015). How fast and how often: The pharmacokinetics of drug use are decisive in addiction. Neurosci Biobehav Rev, 56: 166–179
https://doi.org/10.1016/j.neubiorev.2015.06.012 pmid: 26116543
3 Anderson S M, Pierce R C (2005). Cocaine-induced alterations in dopamine receptor signaling: implications for reinforcement and reinstatement. Pharmacol Ther, 106(3): 389–403
https://doi.org/10.1016/j.pharmthera.2004.12.004 pmid: 15922019
4 Bardo M T, Bevins R A (2000). Conditioned place preference: what does it add to our preclinical understanding of drug reward? Psychopharmacology (Berl), 153(1): 31–43
https://doi.org/10.1007/s002130000569 pmid: 11255927
5 Beardsley P M, Hauser K F (2014). Glial modulators as potential treatments of psychostimulant abuse. Adv Pharmacol, 69: 1–69
https://doi.org/10.1016/B978-0-12-420118-7.00001-9 pmid: 24484974
6 Beardsley P M, Shelton K L, Hendrick E, Johnson K W (2010). The glial cell modulator and phosphodiesterase inhibitor, AV411 (ibudilast), attenuates prime- and stress-induced methamphetamine relapse. Eur J Pharmacol, 637(1-3): 102–108
https://doi.org/10.1016/j.ejphar.2010.04.010 pmid: 20399770
7 Bell R L, Lopez M F, Cui C, Egli M, Johnson K W, Franklin K M, Becker H C (2015). Ibudilast reduces alcohol drinking in multiple animal models of alcohol dependence. Addict Biol, 20(1): 38–42
https://doi.org/10.1111/adb.12106 pmid: 24215262
8 Bertolino A, Crippa D, di Dio S, Fichte K, Musmeci G, Porro V, Rapisarda V, Sastre-y-Hernández M, Schratzer M (1988). Rolipram versus imipramine in inpatients with major, “minor” or atypical depressive disorder: a double-blind double-dummy study aimed at testing a novel therapeutic approach. Int Clin Psychopharmacol, 3(3): 245–253
https://doi.org/10.1097/00004850-198807000-00006 pmid: 3153712
9 Blednov Y A, Benavidez J M, Black M, Harris R A (2014). Inhibition of phosphodiesterase 4 reduces ethanol intake and preference in C57BL/6J mice. Front Neurosci, 8: 129
https://doi.org/10.3389/fnins.2014.00129 pmid: 24904269
10 Britt J P, Benaliouad F, McDevitt R A, Stuber G D, Wise R A, Bonci A (2012). Synaptic and behavioral profile of multiple glutamatergic inputs to the nucleus accumbens. Neuron, 76(4): 790–803
https://doi.org/10.1016/j.neuron.2012.09.040 pmid: 23177963
11 Carlezon W A Jr, Chartoff E H (2007). Intracranial self-stimulation (ICSS) in rodents to study the neurobiology of motivation. Nat Protoc, 2(11): 2987–2995
https://doi.org/10.1038/nprot.2007.441 pmid: 18007634
12 Cherry J A, Davis R L (1999). Cyclic AMP phosphodiesterases are localized in regions of the mouse brain associated with reinforcement, movement, and affect. J Comp Neurol, 407(2): 287–301
https://doi.org/10.1002/(SICI)1096-9861(19990503)407:2<287::AID-CNE9>3.0.CO;2-R pmid: 10213096
13 Conrad K L, Louderback K M, Milano E J, Winder D G (2013). Assessment of the impact of pattern of cocaine dosing schedule during conditioning and reconditioning on magnitude of cocaine CPP, extinction, and reinstatement. Psychopharmacology (Berl), 227(1): 109–116
https://doi.org/10.1007/s00213-012-2944-1 pmid: 23269522
14 Conti M, Richter W, Mehats C, Livera G, Park J Y, Jin C (2003). Cyclic AMP-specific PDE4 phosphodiesterases as critical components of cyclic AMP signaling. J Biol Chem, 278(8): 5493–5496
https://doi.org/10.1074/jbc.R200029200 pmid: 12493749
15 Crabbe J C (2014). Rodent models of genetic contributions to motivation to abuse alcohol. Nebr Symp Motiv, 61: 5–29
https://doi.org/10.1007/978-1-4939-0653-6_2 pmid: 25306777
16 Diamant Z, Spina D (2011). PDE4-inhibitors: a novel, targeted therapy for obstructive airways disease. Pulm Pharmacol Ther, 24(4): 353–360
https://doi.org/10.1016/j.pupt.2010.12.011 pmid: 21255672
17 Fleischhacker W W H, Hinterhuber H, Bauer H, Pflug B, Berner P, Simhandl C, Wolf R, Gerlach W, Jaklitsch H, Sastre-y-Hernández M, Schmeding-Wiegel H, Sperner-Unterweger B, Voet B, Schubert H (1992). A multicenter double-blind study of three different doses of the new cAMP-phosphodiesterase inhibitor rolipram in patients with major depressive disorder. Neuropsychobiology, 26(1-2): 59–64
https://doi.org/10.1159/000118897 pmid: 1475038
18 Franklin K M, Hauser S R, Lasek A W, McClintick J, Ding Z M, McBride W J, Bell R L (2015). Reduction of alcohol drinking of alcohol-preferring (P) and high-alcohol drinking (HAD1) rats by targeting phosphodiesterase-4 (PDE4). Psychopharmacology (Berl), 232(13): 2251–2262
https://doi.org/10.1007/s00213-014-3852-3 pmid: 25585681
19 Gisondi P, Girolomoni G (2016). Apremilast in the therapy of moderate-to-severe chronic plaque psoriasis. Drug Des Devel Ther, 10: 1763–1770
https://doi.org/10.2147/DDDT.S108115 pmid: 27307707
20 González-Cuello A, Sánchez L, Hernández J, Teresa Castells M, Victoria Milanés M, Laorden M L (2007). Phosphodiesterase 4 inhibitors, rolipram and diazepam block the adaptive changes observed during morphine withdrawal in the heart. Eur J Pharmacol, 570(1-3): 1–9
https://doi.org/10.1016/j.ejphar.2007.05.051 pmid: 17601555
21 Graybiel A M (1990). Neurotransmitters and neuromodulators in the basal ganglia. Trends Neurosci, 13(7): 244–254
https://doi.org/10.1016/0166-2236(90)90104-I pmid: 1695398
22 Graybiel A M (2000). The basal ganglia. Curr Biol, 10(14): R509–R511
https://doi.org/10.1016/S0960-9822(00)00593-5 pmid: 10899013
23 Grimm J W, Fyall A M, Osincup D P (2005). Incubation of sucrose craving: effects of reduced training and sucrose pre-loading. Physiol Behav, 84(1): 73–79
https://doi.org/10.1016/j.physbeh.2004.10.011 pmid: 15642609
24 Grimm J W, Hope B T, Wise R A, Shaham Y (2001). Neuroadaptation. Incubation of cocaine craving after withdrawal. Nature, 412(6843): 141–142
https://doi.org/10.1038/35084134 pmid: 11449260
25 Hagen T J, Mo X, Burgin A B, Fox D 3rd, Zhang Z, Gurney M E (2014). Discovery of triazines as selective PDE4B versus PDE4D inhibitors. Bioorg Med Chem Lett, 24(16): 4031–4034
https://doi.org/10.1016/j.bmcl.2014.06.002 pmid: 24998378
26 Hamdy M M, Mamiya T, Noda Y, Sayed M, Assi A A, Gomaa A, Yamada K, Nabeshima T (2001). A selective phosphodiesterase IV inhibitor, rolipram blocks both withdrawal behavioral manifestations, and c-Fos protein expression in morphine dependent mice. Behav Brain Res, 118(1): 85–93
https://doi.org/10.1016/S0166-4328(00)00315-6 pmid: 11163637
27 Hansen R T 3rd, Zhang H T (2015). Phosphodiesterase-4 modulation as a potential therapeutic for cognitive loss in pathological and non-pathological aging: possibilities and pitfalls. Curr Pharm Des, 21(3): 291–302
pmid: 25159075
28 Hiroi N, Nestler E J (1998). Nuclear memory: gene transcription and behavior. Adv Pharmacol, 42: 1037–1041
https://doi.org/10.1016/S1054-3589(08)60924-2 pmid: 9328075
29 Horn C C, Kimball B A, Wang H, Kaus J, Dienel S, Nagy A, Gathright G R, Yates B J, Andrews P L (2013). Why can’t rodents vomit? A comparative behavioral, anatomical, and physiological study. PLoS ONE, 8(4): e60537
https://doi.org/10.1371/journal.pone.0060537 pmid: 23593236
30 Howlett, A. C. (2005). “Cannabinoid receptor signaling.” Handb Exp Pharmacol(168): 53–79.
31 Hu W, Lu T, Chen A, Huang Y, Hansen R, Chandler L J, Zhang H T (2011). Inhibition of phosphodiesterase-4 decreases ethanol intake in mice. Psychopharmacology (Berl), 218(2): 331–339
https://doi.org/10.1007/s00213-011-2290-8 pmid: 21509503
32 Ikemoto S, Bonci A (2014). Neurocircuitry of drug reward. Neuropharmacology, 76 Pt B: 329–341
33 Itzhak Y, Anderson K L (2012). Changes in the magnitude of drug-unconditioned stimulus during conditioning modulate cocaine-induced place preference in mice. Addict Biol, 17(4): 706–716
https://doi.org/10.1111/j.1369-1600.2011.00334.x pmid: 21507159
34 Iyo M, Bi Y, Hashimoto K, Inada T, Fukui S (1996). Prevention of methamphetamine-induced behavioral sensitization in rats by a cyclic AMP phosphodiesterase inhibitor, rolipram. Eur J Pharmacol, 312(2): 163–170
https://doi.org/10.1016/0014-2999(96)00479-7 pmid: 8894591
35 Janes A C, Kantak K M, Cherry J A (2009). The involvement of type IV phosphodiesterases in cocaine-induced sensitization and subsequent pERK expression in the mouse nucleus accumbens. Psychopharmacology (Berl), 206(2): 177–185
https://doi.org/10.1007/s00213-009-1594-4 pmid: 19588125
36 Johansson E M, Reyes-Irisarri E, Mengod G (2012). Comparison of cAMP-specific phosphodiesterase mRNAs distribution in mouse and rat brain. Neurosci Lett, 525(1): 1–6
https://doi.org/10.1016/j.neulet.2012.07.050 pmid: 22884617
37 Kauer J A (2004). Learning mechanisms in addiction: synaptic plasticity in the ventral tegmental area as a result of exposure to drugs of abuse. Annu Rev Physiol, 66(1): 447–475
https://doi.org/10.1146/annurev.physiol.66.032102.112534 pmid: 14977410
38 Kimura M, Tokumura M, Itoh T, Inoue O, Abe K (2006). Lack of cyclic AMP-specific phosphodiesterase 4 activation during naloxone-precipitated morphine withdrawal in rats. Neurosci Lett, 404(1-2): 107–111
https://doi.org/10.1016/j.neulet.2006.05.014 pmid: 16753260
39 Kimura S, Ohi Y, Haji A (2015). Blockade of phosphodiesterase 4 reverses morphine-induced ventilatory disturbance without loss of analgesia. Life Sci, 127: 32–38
https://doi.org/10.1016/j.lfs.2015.02.006 pmid: 25744400
40 Knapp C M, Foye M M, Ciraulo D A, Kornetsky C (1999). The type IV phosphodiesterase inhibitors, Ro 20-1724 and rolipram, block the initiation of cocaine self-administration. Pharmacol Biochem Behav, 62(1): 151–158
https://doi.org/10.1016/S0091-3057(98)00154-3 pmid: 9972858
41 Knapp C M, Lee K, Foye M, Ciraulo D A, Kornetsky C (2001). Additive effects of intra-accumbens infusion of the cAMP-specific phosphodiesterase inhibitor, rolipram and cocaine on brain stimulation reward. Life Sci, 69(14): 1673–1682
https://doi.org/10.1016/S0024-3205(01)01249-8 pmid: 11589507
42 Kuroiwa M, Snyder G L, Shuto T, Fukuda A, Yanagawa Y, Benavides D R, Nairn A C, Bibb J A, Greengard P, Nishi A (2012). Phosphodiesterase 4 inhibition enhances the dopamine D1 receptor/PKA/DARPP-32 signaling cascade in frontal cortex. Psychopharmacology (Berl), 219(4): 1065–1079
https://doi.org/10.1007/s00213-011-2436-8 pmid: 21833500
43 Lai M, Zhu H, Sun A, Zhuang D, Fu D, Chen W, Zhang H T, Zhou W (2014). The phosphodiesterase-4 inhibitor rolipram attenuates heroin-seeking behavior induced by cues or heroin priming in rats. Int J Neuropsychopharmacol, 17(9): 1397–1407
https://doi.org/10.1017/S1461145714000595 pmid: 24832929
44 Lakics V, Karran E H, Boess F G (2010). Quantitative comparison of phosphodiesterase mRNA distribution in human brain and peripheral tissues. Neuropharmacology, 59(6): 367–374
https://doi.org/10.1016/j.neuropharm.2010.05.004 pmid: 20493887
45 Lamontagne S, Meadows E, Luk P, Normandin D, Muise E, Boulet L, Pon D J, Robichaud A, Robertson G S, Metters K M, Nantel F (2001). Localization of phosphodiesterase-4 isoforms in the medulla and nodose ganglion of the squirrel monkey. Brain Res, 920(1-2): 84–96
https://doi.org/10.1016/S0006-8993(01)03023-2 pmid: 11716814
46 Liddie S, Anderson K L, Paz A, Itzhak Y (2012). The effect of phosphodiesterase inhibitors on the extinction of cocaine-induced conditioned place preference in mice. J Psychopharmacol, 26(10): 1375–1382
https://doi.org/10.1177/0269881112447991 pmid: 22596207
47 Lim Y W, Meyer N P, Shah A S, Budde M D, Stemper B D, Olsen C M (2015). Voluntary Alcohol Intake following Blast Exposure in a Rat Model of Mild Traumatic Brain Injury. PLoS ONE, 10(4): e0125130
https://doi.org/10.1371/journal.pone.0125130 pmid: 25910266
48 Liu X, Liu Y, Zhong P, Wilkinson B, Qi J, Olsen C M, Bayer K U, Liu Q S (2014). CaMKII activity in the ventral tegmental area gates cocaine-induced synaptic plasticity in the nucleus accumbens. Neuropsychopharmacology, 39(4): 989–999
https://doi.org/10.1038/npp.2013.299 pmid: 24154664
49 Logrip M L (2015). Phosphodiesterase regulation of alcohol drinking in rodents. Alcohol, 49(8): 795–802
https://doi.org/10.1016/j.alcohol.2015.03.007 pmid: 26095589
50 Logrip M L, Vendruscolo L F, Schlosburg J E, Koob G F, Zorrilla E P (2014). Phosphodiesterase 10A regulates alcohol and saccharin self-administration in rats. Neuropsychopharmacology, 39(7): 1722–1731
https://doi.org/10.1038/npp.2014.20 pmid: 24549104
51 Lu L, Grimm J W, Hope B T, Shaham Y (2004). Incubation of cocaine craving after withdrawal: a review of preclinical data. Neuropharmacology, 47(Suppl 1): 214–226
https://doi.org/10.1016/j.neuropharm.2004.06.027 pmid: 15464139
52 Lugnier C (2006). Cyclic nucleotide phosphodiesterase (PDE) superfamily: a new target for the development of specific therapeutic agents. Pharmacol Ther, 109(3): 366–398
https://doi.org/10.1016/j.pharmthera.2005.07.003 pmid: 16102838
53 MacKenzie S J, Houslay M D (2000). Action of rolipram on specific PDE4 cAMP phosphodiesterase isoforms and on the phosphorylation of cAMP-response-element-binding protein (CREB) and p38 mitogen-activated protein (MAP) kinase in U937 monocytic cells. Biochem J, 347(Pt 2): 571–578
https://doi.org/10.1042/bj3470571 pmid: 10749688
54 Mamiya T, Noda Y, Ren X, Hamdy M, Furukawa S, Kameyama T, Yamada K, Nabeshima T (2001). Involvement of cyclic AMP systems in morphine physical dependence in mice: prevention of development of morphine dependence by rolipram, a phosphodiesterase 4 inhibitor. Br J Pharmacol, 132(5): 1111–1117
https://doi.org/10.1038/sj.bjp.0703912 pmid: 11226142
55 Mantsch J R, Baker D A, Funk D, Lê A D, Shaham Y (2016). Stress-Induced Reinstatement of Drug Seeking: 20 Years of Progress. Neuropsychopharmacology, 41(1): 335–356
https://doi.org/10.1038/npp.2015.142 pmid: 25976297
56 McGirr A, Lipina T V, Mun H S, Georgiou J, Al-Amri A H, Ng E, Zhai D, Elliott C, Cameron R T, Mullins J G, Liu F, Baillie G S, Clapcote S J, Roder J C (2016). Specific Inhibition of Phosphodiesterase-4B Results in Anxiolysis and Facilitates Memory Acquisition. Neuropsychopharmacology, 41(4): 1080–1092
https://doi.org/10.1038/npp.2015.240 pmid: 26272049
57 Mori F, Pérez-Torres S, De Caro R, Porzionato A, Macchi V, Beleta J, Gavaldà A, Palacios J M, Mengod G (2010). The human area postrema and other nuclei related to the emetic reflex express cAMP phosphodiesterases 4B and 4D. J Chem Neuroanat, 40(1): 36–42
https://doi.org/10.1016/j.jchemneu.2010.03.004 pmid: 20347962
58 Mori T, Baba J, Ichimaru Y, Suzuki T (2000). Effects of rolipram, a selective inhibitor of phosphodiesterase 4, on hyperlocomotion induced by several abused drugs in mice. Jpn J Pharmacol, 83(2): 113–118
https://doi.org/10.1254/jjp.83.113 pmid: 10928323
59 Muelbl M J,Nawarawong N N, Clancy P T, Nettesheim C E, Lim Y W,Olsen C M (2016). Responses to drugs of abuse and non-drug rewards in leptin deficient ob/ob mice. Psychopharmacology (Berl),233(14):2799–2811
60 Mulhall A M, Droege C A, Ernst N E, Panos R J, Zafar M A (2015). Phosphodiesterase 4 inhibitors for the treatment of chronic obstructive pulmonary disease: a review of current and developing drugs. Expert Opin Investig Drugs, 24(12): 1597–1611
https://doi.org/10.1517/13543784.2015.1094054 pmid: 26419847
61 Muschamp J W, Carlezon W A Jr (2013). Roles of nucleus accumbens CREB and dynorphin in dysregulation of motivation. Cold Spring Harb Perspect Med, 3(2): a012005
https://doi.org/10.1101/cshperspect.a012005 pmid: 23293139
62 Naganuma K, Omura A, Maekawara N, Saitoh M, Ohkawa N, Kubota T, Nagumo H, Kodama T, Takemura M, Ohtsuka Y, Nakamura J, Tsujita R, Kawasaki K, Yokoi H, Kawanishi M (2009). Discovery of selective PDE4B inhibitors. Bioorg Med Chem Lett, 19(12): 3174–3176
https://doi.org/10.1016/j.bmcl.2009.04.121 pmid: 19447034
63 Negus S S, Miller L L (2014). Intracranial self-stimulation to evaluate abuse potential of drugs. Pharmacol Rev, 66(3): 869–917
https://doi.org/10.1124/pr.112.007419 pmid: 24973197
64 Nestler E J (2015). Reflections on: “A general role for adaptations in G-Proteins and the cyclic AMP system in mediating the chronic actions of morphine and cocaine on neuronal function. Brain Res
pmid: 26740398
65 Nishi A, Kuroiwa M, Miller D B, O’Callaghan J P, Bateup H S, Shuto T, Sotogaku N, Fukuda T, Heintz N, Greengard P, Snyder G L (2008). Distinct roles of PDE4 and PDE10A in the regulation of cAMP/PKA signaling in the striatum. J Neurosci, 28(42): 10460–10471
https://doi.org/10.1523/JNEUROSCI.2518-08.2008 pmid: 18923023
66 Núñez C, González-Cuello A, Sánchez L, Vargas M L, Milanés M V, Laorden M L (2009). Effects of rolipram and diazepam on the adaptive changes induced by morphine withdrawal in the hypothalamic paraventricular nucleus. Eur J Pharmacol, 620(1-3): 1–8
https://doi.org/10.1016/j.ejphar.2009.08.002 pmid: 19683523
67 O’Donnell J M, Zhang H T (2004). Antidepressant effects of inhibitors of cAMP phosphodiesterase (PDE4). Trends Pharmacol Sci, 25(3): 158–163
https://doi.org/10.1016/j.tips.2004.01.003 pmid: 15019272
68 Olsen C M, Childs D S, Stanwood G D, Winder D G (2010). Operant sensation seeking requires metabotropic glutamate receptor 5 (mGluR5). PLoS ONE, 5(11): e15085
https://doi.org/10.1371/journal.pone.0015085 pmid: 21152045
69 Olsen C M, Winder D G (2006). A method for single-session cocaine self-administration in the mouse. Psychopharmacology (Berl), 187(1): 13–21
https://doi.org/10.1007/s00213-006-0388-1 pmid: 16767412
70 Page C P, Spina D (2012). Selective PDE inhibitors as novel treatments for respiratory diseases. Curr Opin Pharmacol, 12(3): 275–286
https://doi.org/10.1016/j.coph.2012.02.016 pmid: 22497841
71 Pan B, Hillard C J, Liu Q S (2008). D2 dopamine receptor activation facilitates endocannabinoid-mediated long-term synaptic depression of GABAergic synaptic transmission in midbrain dopamine neurons via cAMP-protein kinase A signaling. J Neurosci, 28(52): 14018–14030
https://doi.org/10.1523/JNEUROSCI.4035-08.2008 pmid: 19109485
72 Pan B, Hillard C J, Liu Q S (2008). Endocannabinoid signaling mediates cocaine-induced inhibitory synaptic plasticity in midbrain dopamine neurons. J Neurosci, 28(6): 1385–1397
https://doi.org/10.1523/JNEUROSCI.4033-07.2008 pmid: 18256258
73 Pan B, Zhong P, Sun D, Liu Q S (2011). Extracellular signal-regulated kinase signaling in the ventral tegmental area mediates cocaine-induced synaptic plasticity and rewarding effects. J Neurosci, 31(31): 11244–11255
https://doi.org/10.1523/JNEUROSCI.1040-11.2011 pmid: 21813685
74 Pérez-Cadahía B, Drobic B, Davie J R (2011). Activation and function of immediate-early genes in the nervous system. Biochem Cell Biol, 89(1): 61–73
pmid: 21326363
75 Pérez-Torres S, Miró X, Palacios J M, Cortés R, Puigdoménech P, Mengod G (2000). Phosphodiesterase type 4 isozymes expression in human brain examined by in situ hybridization histochemistry and[3H]rolipram binding autoradiography. Comparison with monkey and rat brain. J Chem Neuroanat, 20(3-4): 349–374
https://doi.org/10.1016/S0891-0618(00)00097-1 pmid: 11207431
76 Pierce R C, Kalivas P W (1997). A circuitry model of the expression of behavioral sensitization to amphetamine-like psychostimulants. Brain Res Brain Res Rev, 25(2): 192–216
https://doi.org/10.1016/S0165-0173(97)00021-0 pmid: 9403138
77 Richter W, Menniti F S, Zhang H T, Conti M (2013). PDE4 as a target for cognition enhancement. Expert Opin Ther Targets, 17(9): 1011–1027
https://doi.org/10.1517/14728222.2013.818656 pmid: 23883342
78 Robichaud A, Stamatiou P B, Jin S L, Lachance N, MacDonald D, Laliberté F, Liu S, Huang Z, Conti M, Chan C C (2002). Deletion of phosphodiesterase 4D in mice shortens alpha(2)-adrenoceptor-mediated anesthesia, a behavioral correlate of emesis. J Clin Invest, 110(7): 1045–1052
https://doi.org/10.1172/JCI0215506 pmid: 12370283
79 Robinson T E, Berridge K C (1993). The neural basis of drug craving: an incentive-sensitization theory of addiction. Brain Res Brain Res Rev, 18(3): 247–291
https://doi.org/10.1016/0165-0173(93)90013-P pmid: 8401595
80 Robinson T E, Berridge K C (2008). Review. The incentive sensitization theory of addiction: some current issues. Philos Trans R Soc Lond B Biol Sci, 363(1507): 3137–3146
https://doi.org/10.1098/rstb.2008.0093 pmid: 18640920
81 Rodd Z A, Bell R L, Sable H J, Murphy J M, McBride W J (2004). Recent advances in animal models of alcohol craving and relapse. Pharmacol Biochem Behav, 79(3): 439–450
https://doi.org/10.1016/j.pbb.2004.08.018 pmid: 15582015
82 Schroeder J A, Ruta J D, Gordon J S, Rodrigues A S, Foote C C (2012). The phosphodiesterase inhibitor isobutylmethylxanthine attenuates behavioral sensitization to cocaine. Behav Pharmacol, 23(3): 310–314
https://doi.org/10.1097/FBP.0b013e3283536d04 pmid: 22495185
83 Shaham Y, Shalev U, Lu L, De Wit H, Stewart J (2003). The reinstatement model of drug relapse: history, methodology and major findings. Psychopharmacology (Berl), 168(1-2): 3–20
https://doi.org/10.1007/s00213-002-1224-x pmid: 12402102
84 Siuciak J A, McCarthy S A, Chapin D S, Martin A N (2008). Behavioral and neurochemical characterization of mice deficient in the phosphodiesterase-4B (PDE4B) enzyme. Psychopharmacology (Berl), 197(1): 115–126
https://doi.org/10.1007/s00213-007-1014-6 pmid: 18060387
85 Snider S E, Hendrick E S, Beardsley P M (2013). Glial cell modulators attenuate methamphetamine self-administration in the rat. Eur J Pharmacol, 701(1-3): 124–130
https://doi.org/10.1016/j.ejphar.2013.01.016 pmid: 23375937
86 Snider S E, Vunck S A, van den Oord E J, Adkins D E, McClay J L, Beardsley P M (2012). The glial cell modulators, ibudilast and its amino analog, AV1013, attenuate methamphetamine locomotor activity and its sensitization in mice. Eur J Pharmacol, 679(1-3): 75–80
https://doi.org/10.1016/j.ejphar.2012.01.013 pmid: 22306241
87 Stolerman I P, Childs E, Ford M M, Grant K A (2011). Role of training dose in drug discrimination: a review. Behav Pharmacol, 22(5-6): 415–429
https://doi.org/10.1097/FBP.0b013e328349ab37 pmid: 21808191
88 Sun A, Zhuang D, Zhu H, Lai M, Chen W, Liu H, Zhang F, Zhou W (2015). Decrease of phosphorylated CREB and ERK in nucleus accumbens is associated with the incubation of heroin seeking induced by cues after withdrawal. Neurosci Lett, 591: 166–170
https://doi.org/10.1016/j.neulet.2015.02.048 pmid: 25711798
89 Thompson B E, Sachs B D, Kantak K M, Cherry J A (2004). The Type IV phosphodiesterase inhibitor rolipram interferes with drug-induced conditioned place preference but not immediate early gene induction in mice. Eur J Neurosci, 19(9): 2561–2568
https://doi.org/10.1111/j.0953-816X.2004.03357.x pmid: 15128409
90 Thomsen M, Caine S B (2005). Chronic intravenous drug self-administration in rats and mice. Curr Protoc Neurosci, 32:9.20:9.20.1–9.20.40
https://doi.org/10.1002/0471142301.ns0920s32
91 Todd T P, Vurbic D, Bouton M E (2014). Behavioral and neurobiological mechanisms of extinction in Pavlovian and instrumental learning. Neurobiol Learn Mem, 108: 52–64
https://doi.org/10.1016/j.nlm.2013.08.012 pmid: 23999219
92 Tzschentke T M (2007). Measuring reward with the conditioned place preference (CPP) paradigm: update of the last decade. Addict Biol, 12(3-4): 227–462
https://doi.org/10.1111/j.1369-1600.2007.00070.x pmid: 17678505
93 Wang Z Z, Zhang Y, Zhang H T, Li Y F (2015). Phosphodiesterase: an interface connecting cognitive deficits to neuropsychiatric and neurodegenerative diseases. Curr Pharm Des, 21(3): 303–316
https://doi.org/10.2174/1381612820666140826115559 pmid: 25159069
94 Wen R T, Feng W Y, Liang J H, Zhang H T (2015). Role of phosphodiesterase 4-mediated cyclic AMP signaling in pharmacotherapy for substance dependence. Curr Pharm Des, 21(3): 355–364
https://doi.org/10.2174/1381612820666140826114412 pmid: 25159074
95 Wen R T, Zhang M, Qin W J, Liu Q, Wang W P, Lawrence A J, Zhang H T, Liang J H (2012). The phosphodiesterase-4 (PDE4) inhibitor rolipram decreases ethanol seeking and consumption in alcohol-preferring Fawn-Hooded rats. Alcohol Clin Exp Res, 36(12): 2157–2167
https://doi.org/10.1111/j.1530-0277.2012.01845.x pmid: 22671516
96 Yan Y, Nitta A, Mizuno T, Nakajima A, Yamada K, Nabeshima T (2006). Discriminative-stimulus effects of methamphetamine and morphine in rats are attenuated by cAMP-related compounds. Behav Brain Res, 173(1): 39–46
https://doi.org/10.1016/j.bbr.2006.05.029 pmid: 16857277
97 Young R (2009). Drug Discrimination. In: Buccafusco J J, editor. Source Methods of Behavior Analysis in Neuroscience. 2nd edition. Boca Raton (FL): CRC Press/Taylor & Francis
98 Zhang H T (2009). Cyclic AMP-specific phosphodiesterase-4 as a target for the development of antidepressant drugs. Curr Pharm Des, 15(14): 1688–1698
https://doi.org/10.2174/138161209788168092 pmid: 19442182
99 Zhang H T, Huang Y, Masood A, Stolinski L R, Li Y, Zhang L, Dlaboga D, Jin S L, Conti M, O’Donnell J M (2008). Anxiogenic-like behavioral phenotype of mice deficient in phosphodiesterase 4B (PDE4B). Neuropsychopharmacology, 33(7): 1611–1623
https://doi.org/10.1038/sj.npp.1301537 pmid: 17700644
100 Zhong P, Wang W, Yu F, Nazari M, Liu X, Liu Q S (2012). Phosphodiesterase 4 inhibition impairs cocaine-induced inhibitory synaptic plasticity and conditioned place preference. Neuropsychopharmacology, 37(11): 2377–2387
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed