cAMP-dependent protein kinase and reward-related learning: intra-accumbens Rp-cAMPS blocks amphetamine-produced place conditioning in rats.

摘要

RATIONALE. Dopamine may produce reward-related learning by activating D(1)-like receptors in the nucleus accumbens (NAc) and stimulating the formation of cyclic adenosine monophosphate (cAMP) and the activation of cAMP-dependent protein kinase (PKA). OBJECTIVES. This hypothesis was tested using the conditioned place preference (CPP) based on NAc injections of amphetamine (amph) and evaluating the effects of PKA inhibition with Rp-cAMPS. METHODS. The CPP procedure consisted of three phases: pre-exposure (three 15-min sessions in a chamber consisting of two distinct compartments connected by a tunnel), conditioning (four 30-min placements into one compartment with the tunnel blocked following drug injection into the NAc alternating with four similar placements into the other side following NAc injection of saline), and test (one 15-min session with the tunnel open). A CPP was defined as an increase in time spent on the drug-paired side from mean pre-exposure to test. RESULTS. Dose-response experiments showed that 15.0 or 20.0 but not 5.0 or 10.0 micro g/0.5 micro l per side of amph produced a CPP. The amph (20.0 micro g) CPP was blocked by Rp-cAMPS co-injections of 25.0 and 250 but not 2.5 ng/0.5 micro l per side. Rp-cAMPS or the PKA activator Sp-cAMPS (50.0, 250, 500, 600 ng/0.5 micro l per side) alone had no effect on side preference. Co-injection of 10.0 micro g amph+Sp-cAMPS (25.0, 50.0, 250, 500 ng) did not result in a CPP but co-injection of 20.0 micro g amph+Sp-cAMPS (250 ng) led to a loss of the CPP normally seen with that dose of amph. Doses of Rp-cAMPS that blocked CPP did not block the locomotor stimulatory effect of amph during conditioning sessions. CONCLUSIONS. Results supported the hypothesis that PKA activation in NAc is necessary for reward-related learning.