Abstract

Introduction

Materials & Methods

Results

Discussion & Conclusion

References

Discussion
Board

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