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Conditioned locomotion in rats following amphetamine infusion into the nucleus accumbens: blockade by coincident inhibition of protein kinase A

Recent studies demonstrate a role for cyclic adenosine monophosphate (cAMP)‐dependent protein kinase (PKA) in the nucleus accumbens (NAc) in reward‐related learning. To clarify this role, we assessed the effect of PKA inhibition on the unconditioned and conditioned locomotor activating properties of intra‐NAc amphetamine. Rats underwent three 60 min conditioning sessions, pairing a test environment with bilateral co‐infusions of amphetamine (25 μg/side) and the PKA inhibitor Rp‐adenosine 3′,5′‐cyclic monophosphothioate triethylamine (Rp‐cAMPS) (0, 2.5, 250, 500 ng, 1, 10 or 20 μg/side). Two additional groups – receiving amphetamine explicitly unpaired with the environment or saline/environment pairings – served as controls. In a subsequent drug‐free 60 min session, animals that received amphetamine/environment pairings demonstrated conditioned locomotion relative to controls. Rp‐cAMPS co‐treatment during pairing sessions differentially affected conditioned and unconditioned locomotor activation. Amphetamine‐induced unconditioned activity was significantly enhanced by 500 ng and 1 μg Rp‐cAMPS, locomotor sensitization was enhanced by 250 ng–1 μg Rp‐cAMPS, and conditioned activity was attenuated by 1 μg Rp‐cAMPS and blocked by 10 and 20 μg Rp‐cAMPS. Thus, unconditioned activity and locomotor sensitization were enhanced at doses (250 ng–1 μg) that did not affect or attenuated conditioned activity, while conditioned activity was reduced or blocked at doses (1–20 μg) that enhanced or did not affect overall unconditioned activity. These results demonstrate that the activation of PKA plays a critical role in the process by which properties of drugs become associated with environmental stimuli.