Effects of systemic or nucleus accumbens-directed dopamine D1 receptor antagonism on sucrose seeking in rats.

RATIONALE: Conditioned cues can elicit relapse to drug- and food-seeking behavior over prolonged periods of abstinence. If seeking behavior depends on mesolimbic dopamine D1 receptors, blocking these receptors should reduce seeking behavior.

OBJECTIVES: We examined the effects of either systemic or intra-nucleus accumbens administration of the D1 antagonist SCH 23390 on extinction responding (sucrose seeking) by rats either 1 or 30 days into forced abstinence.

MATERIALS AND METHODS: Rats self-administered 10% sucrose paired with a tone + light cue for 10 days. After either 1 or 30 days of forced abstinence, rats received systemic (0, 1, 5, or 25 μg/kg IP) or bilateral nucleus accumbens core or shell (0.3 or 0.6 μg/site) injections of SCH 23390 prior to extinction testing.

RESULTS: Saline-treated rats responded more during extinction following 30 vs. 1 day of forced abstinence ("incubation of craving"). Systemic SCH 23390 reduced sucrose seeking after 1 day of forced abstinence, significantly reducing responding following pretreatment with 1, 5, and 25 μg/kg SCH 23390, but only 25 μg/kg significantly reduced sucrose seeking after 30 days of forced abstinence. SCH 23390 (0.3 or 0.6 μg/site) in the core or shell of the nucleus accumbens reduced sucrose seeking in all groups.

CONCLUSION: Nucleus accumbens D1 receptors are involved in sucrose seeking, but it is not clear if they are involved in the incubation of craving. The fact that D1 antagonism reduced sucrose seeking across an extended period of abstinence may be of use for development of treatment strategies for relapse.