D1 RECEPTORS IN THE NUCLEUS ACCUMBENS-SHELL, BUT NOT THE CORE, ARE INVOLVED IN MEDIATING ETHANOL-SEEKING BEHAVIOR OF ALCOHOL-PREFERRING (P) RATS

Clinical and preclinical research suggest that activation of the mesolimbic dopamine (DA) system is involved in mediating the rewarding actions of drugs of abuse, as well as promoting drug-seeking behavior. Inhibition of DA D-1 receptors in the nucleus accumbens (Acb) can reduce ethanol (EtOH)-seeking behavior of nonselective rats triggered by environmental context. However, to date, there has been no research on the effects of D-1 receptor agents on EtOH-seeking behavior of high alcohol-preferring (P) rats following prolonged abstinence. The objective of the present study was to examine the effects of microinjecting the D-1 antagonist SCH 23390 or the D-1 agonist A-77636 into the Acb shell or Acb core on spontaneous recovery of EtOH-seeking behavior. After 10 weeks of concurrent access to EtOH and water, P rats underwent seven extinction sessions (EtOH and water withheld), followed by 2 weeks in their home cages without access to EtOH or operant sessions. In the 2nd week of the home cage phase, rats were bilaterally implanted with guide cannula aimed at the Acb shell or Acb core; rats were allowed 7 days to recover before EtOH-seeking was assessed by the Pavlovian Spontaneous Recovery (PSR) model. Administration of SCH23390 (1 mu g/side) into the Acb shell inhibited responding on the EtOH lever, whereas administration of A-77636 (0.125 mu g/side) increased responding on the EtOH lever. Microinfusion of D-1 receptor agents into the Acb core did not alter responding on the EtOH lever. Responses on the water lever were not altered by any of the treatments. The results suggest that activation of D-1 receptors within the Acb shell, but not Acb core, are involved in mediating PSR of EtOH-seeking behavior of P rats. (C) 2015 IBRO. Published by Elsevier Ltd. All rights reserved.