Possible cholinergic-dopaminergic link in memory facilitation induced by oxotremorine in mice

The immediate post-trial injection of the centrally active muscarinic agonist oxotremorine (0.025, 0.050 and 0.100 mg/kg, IP) can facilitate the retention of a passive-avoidance response in mice, as indicated by performance on a retention test 24 h later. Injections given 10 min after training also significantly facilitated retention, but given 120 min after training did not affect retention. These findings suggest an action of oxotremorine on memory mechanisms. The enhanced retention was neither the result of a punishing effect of oxotremorine nor of a nonspecific proactive pharmacological action of the drug. The memory facilitation produced by oxotremorine (0.050 mg/kg, IP) was not antagonized by pretreatment with phentolamine (10 mg/kg, 30 min, IP), phenoxybenzamine (10 mg/kg, 120 min, IP) or piperoxane (20 mg/kg, 30 min, IP). The alpha-noradrenergic blocking agents had no effect by themselves. On the other hand, the immediate post-trial injection of oxotremorine (0.050 mg/kg, IP) did not enhance retention when mice were pretreated with haloperidol (0.5 mg/kg, 120 min, IP). Haloperidol injected either before training or before the retention test did not alter performance during the retention test. This suggests that haloperidol impairs neither acquisition of the avoidance response nor its retrieval. Thus, it is probable that haloperidol pretreatment impaired oxotremorine-induced memory facilitation. We suggest a possible participation of brain catecholamines in memory facilitation induced by oxotremorine in mice.