Blocking Dopamine D1-Like Receptors Attenuates Context-Induced Renewal of Pavlovian-Conditioned Alcohol-Seeking in Rats

Abstract

Environmental contexts associated with drug use can trigger craving in humans and the renewal of drug-seeking behaviors in animals. Here, we tested the hypothesis that context-induced renewal of Pavlovian-conditioned alcohol-seeking is mediated by dopamine. Male, Long-Evans rats were trained to discriminate between two, 10-second, auditory conditioned stimuli. One stimulus (CS+) was consistently paired with 15% ethanol (EtOH) (v/v, 0.2ml per CS+) and the second stimulus (CS-) was not. Each CS occurred 16 times per session, and entries into a fluid port where EtOH was delivered were measured. Pavlovian discrimination training (PDT) occurred in a distinctive context, referred to as Context A. Subsequently, behavior was extinguished by presenting both cues without EtOH in a different context (Context B). At test, rats were injected with a dopamine D1-like receptor antagonist (R)-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride (SCH 23390; 0, 3.33, 10μg/kg; 1ml/kg; s.c.) and presented with the CS+ and CS- without EtOH in the prior PDT context (Context A). Across training, rats developed higher response levels to the alcohol-predictive CS+, compared with the CS-. Port entries during the CS+ decreased across extinction. At test, placement into the alcohol-associated context triggered a selective increase in CS+ responses after saline, which was significantly reduced by SCH 23390 pretreatment. In separate studies, SCH 23390 did not affect lever-pressing for sucrose under reinforced or extinction conditions, but decreased port entries relative to saline in both cases. These data indicate that dopamine is required for context-induced renewal of Pavlovian-conditioned alcohol-seeking and may also be necessary for preparatory conditioned approach behaviors.