Effects of alcohol and lorazepam during extinction of alcohol self-administration in rats.

Systemic injections of alcohol have previously been reported to 'prime' or to reinstate self-administration of alcohol in rats, and it has been suggested that the priming effects of drugs are related to their stimulus properties. We tested this hypothesis by investigating the effects of lorazepam, which cross-generalizes with alcohol in animal drug-discrimination studies, in rats trained to self-administer 7% alcohol in an operant paradigm. Once animals were trained, extinction tests were carried out twice weekly, before which rats were injected with either vehicle, alcohol (0.063-0.5 g/kg, i.p.) or lorazepam (0.03-0.25 mg/kg, i.p.). Alcohol did not increase responding for alcohol during extinction. Doses of 0.25 and 0.5 g/kg reduced alcohol-appropriate lever pressing (p < 0.05 versus 0 g/kg), with the largest dose also suppressing general activity (p < 0.02 versus 0 g/kg). Lorazepam also reduced alcohol-appropriate responding, in a behaviourally specific manner; doses of 0.03 mg/kg and above decreased lever pressing (p < 0.05 versus 0 mg/kg), whereas general activity was depressed at 0.06 mg/kg and larger doses (p < 0.05 versus 0 mg/kg). Although lorazepam mimicked the effect of alcohol at doses predicted to do so on the basis of their relative potency in drug discrimination studies, neither alcohol nor lorazepam primed rats to respond for alcohol. By contrast, the pattern of results suggested that, in this model, they 'satiated' or substituted for alcohol, resulting in a reduced motivation to respond.