Invited Symposium: Perspectives on Behavioural Function of Dopamine in the Nucleus Accumbens



Materials & Methods


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Accumbens Amphetamine-Produced Reward Depends on cAMP-Dependent Protein Kinase

Beninger, R.J. (Dept. Psychology, Queen's University, Canada)
Aujla, H. (Dept. Psychology, Queen's University, Canada)
McGibney, K. (Dept. Psychology, Queen's University, Canada)
Nakonechny, P.L. (Dept. Psychology, Queen's University, Canada)
Savina, J. (Dept. Psychology, Queen's University, Canada)
Smith, I.D. (Dept. Psychology, Queen's University, Canada)
Sutton, M.A. (Dept. Psychology, Queen's University, Canada)
Westly, J.K. (Dept. Psychology, Queen's University, Canada)

Contact Person: Richard J. Beninger (beninger@psyc.queensu.ca)


Many recent data implicate D1-like receptors in dopamine (DA)-mediated reward-related learning suggesting that DA may produce learning by activating adenylyl cyclase and the cyclic adenosine monophosphate (cAMP) pathway. To evaluate this hypothesis we manipulated cAMP-dependent protein kinase (PKA) in the nucleus accumbens (NAcc) in DA-dependent learning paradigms. Thus, bilateral intra-NAcc injections of amphetamine (amphet) produced place conditioning and co-injection of the PKA inhibitor Rp-cAMPS with amphet blocked this effect in spite of actually increasing the locomotor stimulant effects of amphet. Injection of the same doses of Rp-cAMPS alone produced no significant effects. Intra-NAcc injections of the PKA activator Sp-cAMPS also impaired amphet-produced place conditioning. In another study, bilateral intra-NAcc injections of amphet over three days led to conditioned activity on a drug free test day and co-injection of Rp-cAMPS with amphet blocked the effect at doses that did not reduce amphet's locomotor stimulant effect. Additionally, Rp-cAMPS injected with amphet into the NAcc impaired the enhancement of responding for conditioned reward but not the stimulant effect. In a final study, preliminary results suggest that Rp-cAMPS in the frontal cortex may impair working memory required for a spatial win-shift task in the radial maze. These results support the hypothesis that activation of the cAMP pathway by DA acting at D1-like receptors leads to learning. (Funded by N.S.E.R.C.)

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Presentation Number SAbeninger0689
Keywords: accumbens, PKA, dopamine, reward, Rp-cAMPS

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Beninger, R.J.; Aujla, H.; McGibney, K.; Nakonechny, P.L.; Savina, J.; Smith, I.D.; Sutton, M.A.; Westly, J.K.; (1998). Accumbens Amphetamine-Produced Reward Depends on cAMP-Dependent Protein Kinase. Presented at INABIS '98 - 5th Internet World Congress on Biomedical Sciences at McMaster University, Canada, Dec 7-16th. Invited Symposium. Available at URL http://www.mcmaster.ca/inabis98/salamone/beninger0689/index.html
© 1998 Author(s) Hold Copyright