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8-pCPT, an Epac activator, impairs conditioned place preference based on nucleus accumbens amphetamine in rats

Published online by Cambridge University Press:  01 August 2013

Sung Woo Park ,
Ali Roohbakhsh  and
Richard J. Beninger
Sung Woo Park
Affiliation:
Centre for Neuroscience Studies, Queen's University, Kingston, ON, Canada
Ali Roohbakhsh
Affiliation:
Pharmaceutical Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
Richard J. Beninger*
Affiliation:
Centre for Neuroscience Studies, Queen's University, Kingston, ON, Canada Department of Psychology, Queen's University, Kingston, ON, Canada Department of Psychiatry, Queen's University, Kingston, ON, Canada
*
Dr. Richard J. Beninger, Department of Psychology, 62 Arch St., Queen's University, Kingston, ON, Canada K7L 3N6. Tel: +1 613 533 2486; Fax: +1 613 533 2499; E-mail: beninger@queensu.ca
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Abstract

Objectives

Dopamine receptor-mediated 3′,5′-cyclic adenosine monophosphate (cAMP)-dependent intracellular signalling is important for reward-related learning. cAMP activates cAMP-dependent protein kinase (PKA) and exchange protein directly activated by cAMP (Epac). We tested the hypothesis that reward-related learning may be mediated by Epac.

Methods

We evaluated conditioned place preference (CPP) on the basis of nucleus accumbens (NAc) injections of amphetamine (20 μg/0.5 μl/side) plus Sp-adenosine 3′,5′-cyclic monophosphorothioate triethylamanine (Sp-cAMPS) (0.1, 1.0, 10, 15, 20 μg/0.5 μl/side), an activator of both PKA and Epac, or amphetamine (20 μg) plus 8-(4-chlorophenylthio)-2′-O-methyladenosine-3′,5′-cyclic monophosphate (8-pCPT) (0.73, 1.27, 1.45, 2.89, 5.78, 11.56 μg/0.5 μl/side), an activator of Epac.

Results

In agreement with previous results, Sp-cAMPS dose-dependently impaired CPP. 8-pCPT impaired CPP at one dose (1.45 μg/0.5 μl/side) and we replicated this effect three times.

Conclusion

The results implicate Epac in the acquisition of reward-related learning.

Keywords

amphetamineexchange protein directly activated by cAMPincentive learningsecond messengers
Type
Original Articles
Information
Acta Neuropsychiatrica , Volume 26 , Issue 2 , April 2014 , pp. 104 - 111
Copyright
Copyright © Scandinavian College of Neuropsychopharmacology 2013 

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References

1.Beninger, RJ, Gerdjikov, T. The role of signaling molecules in reward-related incentive learning. Neurotox Res 2004;6:91–104.CrossRefGoogle ScholarPubMed
2.Abrahams, BS, Rutherford, JD, Mallet, PE, Beninger, RJ. Place conditioning with the dopamine D1-like receptor agonist SKF 82958 but not SKF 81297 or SKF 77434. Eur J Pharmacol 1998;343:111–118.CrossRefGoogle ScholarPubMed
3.Hoffman, DC, Dickson, PR, Beninger, RJ. The dopamine D2 receptor agonists, quinpirole and bromocriptine produce conditioned place preferences. Prog Neuropsychopharmacol Biol Psychiatry 1988;12:315–322.CrossRefGoogle ScholarPubMed
4.Hoffman, DC, Beninger, RJ. The effects of selective dopamine D1 or D2 receptor antagonists on the establishment of agonist-induced place conditioning in rats. Pharmacol Biochem Behav 1989;33:273–279.CrossRefGoogle ScholarPubMed
5.Carr, GD, White, NM. Anatomical disassociation of amphetamine's rewarding and aversive effects: an intracranial microinjection study. Psychopharmacology (Berl) 1986;89:340–346.CrossRefGoogle ScholarPubMed
6.Konradi, C, Cole, RL, Heckers, S, Hyman, SE. Amphetamine regulates gene expression in rat striatum via transcription factor CREB. J Neurosci 1994;14:5623–5634.CrossRefGoogle ScholarPubMed
7.Kawasaki, H, Springett, GM, Mochizuki, Net al. A family of cAMP-binding proteins that directly activate Rap1. Science 1998;282:2275–2279.CrossRefGoogle ScholarPubMed
8.Breckler, M, Berthouze, M, Laurent, AC, Crozatier, B, Morel, E, Lezoualc'h, F. Rap-linked cAMP signaling Epac proteins: compartmentation, functioning and disease implications. Cell Signal 2011;23:1257–1266.CrossRefGoogle ScholarPubMed
9.Huston, E, Lynch, MJ, Mohamed, Aet al. EPAC and PKA allow cAMP dual control over DNA-PK nuclear translocation. Proc Natl Acad Sci U S A 2008;105:12791–12796.CrossRefGoogle ScholarPubMed
10.Helms, MN, Chen, XJ, Ramosevac, S, Eaton, DC, Jain, L. Dopamine regulation of amiloride-sensitive sodium channels in lung cells. Am J Physiol Lung Cell Mol Physiol 2006;290:L710–L722.CrossRefGoogle ScholarPubMed
11.McKnight, GS. Cyclic AMP second messenger systems. Curr Opin Cell Biol 1991;3:213–217.CrossRefGoogle ScholarPubMed
12.Rehmann, H, Schwede, F, Døskeland, SO, Wittinghofer, A, Bos, JL. Ligand-mediated activation of the cAMP-responsive guanine nucleotide exchange factor Epac. J Biol Chem 2003;278:38548–38556.CrossRefGoogle ScholarPubMed
13.Beninger, RJ, Nakonechny, PL, Savina, I. cAMP-dependent protein kinase and reward-related learning: intra-accumbens Rp-cAMPS blocks amphetamine-produced place conditioning in rats. Psychopharmacology (Berl) 2003;170:23–32.CrossRefGoogle ScholarPubMed
14.Lin, SL, Johnson-Farley, NN, Lubinsky, DR, Cowen, DS. Coupling of neuronal 5-HT7 receptors to activation of extracellular-regulated kinase through a protein kinase A-independent pathway that can utilize Epac. J Neurochem 2003;87:1076–1085.CrossRefGoogle ScholarPubMed
15.Mayer, P, Hinze, AV, Harst, A, von Kügelgen, I. A2B receptors mediate the induction of early genes and inhibition of arterial smooth muscle cell proliferation via Epac. Cardiovasc Res 2011;90:148–156.CrossRefGoogle ScholarPubMed
16.Van Kolen, K, Dautzenberg, FM, Verstraeten, Ket al. Corticotropin releasing factor-induced ERK phosphorylation in AtT20 cells occurs via a cAMP-dependent mechanism requiring EPAC2. Neuropharmacology 2010;58:135–144.CrossRefGoogle Scholar
17.Woolfrey, KM, Srivastava, DP, Photowala, Het al. Epac2 induces synapse remodeling and depression and its disease-associated forms alter spines. Nat Neurosci 2009;12:1275–1284.CrossRefGoogle ScholarPubMed
18.Enserink, JM, Christensen, AE, de Rooij, Jet al. A novel Epac-specific cAMP analogue demonstrates independent regulation of Rap1 and ERK. Nat Cell Biol 2002;4:901–906.CrossRefGoogle ScholarPubMed
19.Ma, N, Abel, T, Hernandez, PJ. Exchange protein activated by cAMP enhances long-term memory formation independent of protein kinase A. Learn Mem 2009;16:367–370.CrossRefGoogle ScholarPubMed
20.Jentsch, JD, Olausson, P, Nestler, EJ, Taylor, JR. Stimulation of protein kinase a activity in the rat amygdala enhances reward-related learning. Biol Psychiatry 2002;52:111–118.CrossRefGoogle ScholarPubMed
21.Baldwin, AE, Sadeghian, K, Holahan, MR, Kelley, AE. Appetitive instrumental learning is impaired by inhibition of cAMP-dependent protein kinase within the nucleus accumbens. Neurobiol Learn Mem 2002;77:44–62.CrossRefGoogle ScholarPubMed
22.Ouyang, M, Zhang, L, Zhu, JJ, Schwede, F, Thomas, SA. Epac signaling is required for hippocampus-dependent memory retrieval. Proc Natl Acad Sci U S A 2008;105:11993–11997.CrossRefGoogle ScholarPubMed
23.Dao, KK, Teigen, K, Kopperud, Ret al. Epac1 and cAMP-dependent protein kinase holoenzyme have similar cAMP affinity, but their cAMP domains have distinct structural features and cyclic nucleotide recognition. J Biol Chem 2006;281:21500–21511.CrossRefGoogle ScholarPubMed
24.Baillie, GS, Houslay, MD. Arrestin times for compartmentalised cAMP signaling and phosphodiesterase-4 enzymes. Curr Opin Cell Biol 2005;17:129–134.CrossRefGoogle ScholarPubMed
25.Viste, K, Kopperud, RK, Christensen, AE, Døskeland, SO. Substrate enhances the sensitivity of type I protein kinase a to cAMP. J Biol Chem 2005;280:13279–13284.CrossRefGoogle Scholar
26.Kiermayer, S, Biondi, RM, Imig, Jet al. Epac activation converts cAMP from a proliferative into a differentiation signal in PC12 cells. Mol Biol Cell 2005;16:5639–5648.CrossRefGoogle ScholarPubMed
27.Garay, J, D'Angelo, JA, Park, Yet al. Crosstalk between PKA and Epac regulates the phenotypic maturation and function of human dendritic cells. J Immunol 2010;185:3227–3238.CrossRefGoogle ScholarPubMed
28.Poppe, H, Rybalkin, SD, Rehmann, Het al. Cyclic nucleotide analogs as probes of signaling pathways. Nat Methods 2008;5:277–278.CrossRefGoogle ScholarPubMed
29.Enyeart, JA, Enyeart, JJ. Metabolites of an Epac-selective cAMP analog induce cortisol synthesis by adrenocortical cells through a cAMP-independent pathway. PLoS One 2009;4:e6088.CrossRefGoogle ScholarPubMed