Phosphodiesterase 10A regulates alcohol and saccharin self-administration in rats.

摘要: A history of stress produces increases in rodent relapse-like alcohol self-administration behavior and regional brain gene expression phosphodiesterase 10A (PDE10A), a dual-specificity cyclic adenosine monophosphate/cyclic guanosine monophosphate-inhibiting enzyme. Here, we tested the hypothesis that administration TP-10, specific PDE10A inhibitor, would reduce conditions predisposing to elevated self-administration. TP-10 dose-dependently (0.562, 1.0 mg/kg; subcutaneously) reduced regardless enhancement behavior. also genetically alcohol-preferring rats, as well alcohol-non-dependent -dependent rats. Effective systemic doses did not alter pharmacokinetics, significantly motor activity or intrabout operant response speed, promote conditioned place aversion. saccharin self-administration, suggesting general role for reinforcing substances. inhibition dorsolateral striatum, but nucleus accumbens, Taken together, results implicate striatum facilitating intake support further investigation systems pathophysiology potential treatment substance use disorders.