Nucleus accumbens PKA inhibition blocks acquisition but enhances expression of amphetamine-produced conditioned activity in rats

Abstract

The nucleus accumbens (NAc) plays a central role in dopamine-produced reward-related learning. In previous studies, the cyclic adenosine monophosphate-dependent protein kinase (PKA) inhibitor Rp-Cyclic 3',5'-hydrogen phosphorothioate adenosine triethylammonium salt (Rp-cAMPS) blocked the acquisition but not expression of NAc reward-related learning for natural rewards and the acquisition of psychostimulant drug conditioning. The current study assessed the role of PKA in the expression of NAc amphetamine (amph)-produced conditioning using conditioned activity (CA). After 5 days of habituation, a test environment was paired with bilateral NAc injections of amph (0.0 or 25.0 micro g) and the PKA inhibitor Rp-cAMPS (0.0, 5.0, 10.0, or 20.0 micro g) over three 60-min conditioning sessions separated by 48 h. To test for effects on expression, some groups received vehicle or amph alone before conditioning sessions and were injected with 0.0, 0.25, 5.0, or 20.0 mug of Rp-cAMPS before the single 60-min test session. Amph produced acute increases in locomotion and robust CA. Rp-cAMPS impaired the acquisition of amph-produced CA but not its expression; in fact, it enhanced expression. Results show that PKA inhibition blocks the acquisition but not the expression of amph-produced conditioning.