Intracranial self-stimulation in FAST and SLOW mice: effects of alcohol and cocaine

RATIONALE: Sensitivity to the stimulant and rewarding effects of alcohol may be genetically-correlated traits that predispose individuals to developing an alcohol use disorder. OBJECTIVE: To examine the effects of alcohol and cocaine on intracranial self-stimulation (ICSS) in FAST and SLOW mice, which were selectively bred for extremes in alcohol stimulation. METHODS: Male FAST and SLOW mice were conditioned to respond for reinforcement by direct electrical stimulation of the medial forebrain bundle (i.e. brain stimulation-reward or BSR). ICSS responses were determined immediately before and after oral gavage with water or alcohol (0.3 – 2.4 g/kg) or intraperitoneal injection with saline or cocaine (1.0 – 30.0 mg/kg). In separate FAST and SLOW mice, the locomotor effects of these treatments were measured in activity chambers. RESULTS: Alcohol dose-dependently lowered the threshold for self-stimulation (θ(0)) and the frequency that maintained 50% of maximal responding (EF50) in FAST mice but did not significantly affect these parameters in SLOW mice. The largest effects of alcohol were after the 1.7 and 2.4 g/kg doses and were about 40% compared to water injection. Alcohol did not affect MAX response rates, but dose-dependently stimulated locomotor activity in FAST mice. Cocaine lowered thresholds equally in FAST and SLOW mice, although cocaine- stimulated locomotor activity was higher in the FAST than in the SLOW mice. CONCLUSIONS: Selective breeding for alcohol locomotor stimulation also renders the mice more sensitive to the effects of alcohol, but not cocaine, on ICSS