Post-trial treatment with the nicotinic agonist metanicotine: Differential effects in Wistar rats with high versus...

Laboratory rats, although identical in strain, sex, age and housing conditions, can differ considerably in behavior and physiology. When screened in an open-field, for example, Wistar rats can be assigned to subgroups, based on the measure of rearing activity (high, low rearing activity; HRA/LRA). Such rats have previously been found to differ in dopaminergic and cholinergic brain mechanisms, reactivity to cholinergic drugs, and in tests of learning and memory. Here, we asked whether HRA and LRA rats might respond differently to nicotinic treatment, when given during the consolidation of an aversive experience. Therefore, we tested them for performance in an inhibitory avoidance task where they received post-trial injections of either saline, or the nicotinic agonist metanicotine (RJR-2403, 0.017-1.7 mg/kg, i.p.). In support of previous findings, saline-treated LRA rats showed a trend for higher step-in latencies than HRA rats after shock experience. Furthermore, metanicotine was effective only in LRA rats: Compared to their respective saline-treated controls, the retention scores of LRA rats were decreased after post-trial treatment with the highest dose (1.7 mg/kg). Thus, the nicotinic agonist had an amnestic-like effect dependent on dose and subject-dependent factors (HRA/LRA). These findings are discussed with respect to possible drug actions on mnestic and non-mnestic mechanisms, and the importance of taking subject-dependent variability into account when analysing drug effects.