Behavioural sensitization to a dopamine agonist is associated with reversal of stress-induced anhedonia

Abstract

Chronic exposure to very mild unpredictable stress (CMS) has previously been found to reduce the consumption of palatable sweet solutions and to impair place preference conditioning; evidence has been presented that these effects may reflect a dysfunction of the mesolimbic dopamine system. In the present study, rats were subjected to CMS for a total of 9 weeks. CMS reduced the consumption of a 1% sucrose solution. During weeks 6 and 7, animals received quinpirole (0–400 µg/kg) twice weekly. Both CMS-treated animals and controls showed sensitization to the locomotor stimulant effects of quinpirole. Subsequently, a sustained recovery of sucrose drinking was observed in quinpirole-treated stressed animals. During week 8, all animals received a single pair of place preference conditioning trials, in which quinpirole (200 µg/kg) was administered in a distinctive environment, and vehicle in a different environment. Non-stressed animals showed an increase in preference for the environment associated with quinpirole, as did stressed animals that had been sensitized to quinpirole; this effect was absent in untreated stressed animals. Finally, in week 9, acute administration of raclopride (150 µg/kg) was found to reverse the recovery of sucrose drinking in quinpirole-treated stressed animals, suggesting that these effects are mediated by an increase in dopamine function.