Evidence for a possible interaction between noradrenergic and serotonergic neurotransmission in the retrieval of a previously learned aversive habit in mice.

The present series of experiments examined the effects of pretreating pirenperone-injected mice with a variety of non-serotonergic receptor antagonists on retrieval of a one-trial inhibitory (passive) avoidance task. Water-deprived mice were trained to avoid drinking from a water spout located in the avoidance chamber by pairing foot-shock with licks from the water spout. Retention was measured as the suppression of drinking (latency to drink) 48 h later. Pre-test administration of pirenperone (1.0 mg/kg) significantly enhanced retrieval (increased latencies). The suppression of drinking could not be attributed to the non-specific effects of pirenperone on behavior in general, as the performance of non-contigently shocked mice injected with the same dose of pirenperone did not exhibit a similar elevation in latencies. Of the seven pretreatment drugs examined, only phenoxybenzamine (1.0 mg/kg) completely blocked the pirenperone-induced response. Bicuculline (1.0 mg/kg) partially attenuated the enhanced performance resulting from pre-test pirenperone administration. The results suggest that the pirenperone-induced response may be partly due to activation of noradrenergic (alpha) neurotransmission.