The enhancement of retention induced by vasopressin in mice may be mediated by an activation of central nicotinic cholinergic mechanisms

Immediate post-training subcutaneous administration of lysine vasopressin (LVP, 0.003-1.00 μg/kg) enhanced retention, whereas the vasopressin antagonist AAVP (0.01-0.30 μg/kg) impaired it, in male Swiss mice tested 48 h after training in an inhibitory avoidance task. Both effects were dose-dependent. Neither LVP nor AAVP affected response latencies in mice not given the footshock on the training trial. The simultaneous administration of AAVP at a dose (0.01 μg/kg) which had no effect on retention shifted the dose-response curve of LVP to the right. Nicotine (1.0-30.0 μg/kg, sc), a central nicotinic cholinergic agonist, also facilitated retention in a dose-related manner without affecting the retention performance of unshocked mice. The effect of nicotine was prevented by the central acting nicotinic cholinergic receptor antagonist mecamylamine (5 mg/kg, sc). In contrast, neither hexamethonium (5 mg/kg, sc), a peripheral acting nicotinic receptor blocker, nor atropine (0.5 mg/kg, sc) or methylatropine (0.5 mg/kg, sc), two anticholinergic drugs which are known to act on muscarinic cholinergic receptors, prevented the effect of post-training nicotine. The effects of LVP and nicotine were time-dependent, suggesting that both treatments enhanced retention by influencing post-training processes involved in memory storage. Low doses of nicotine (1.50 μg/kg, sc) or the central anticholinesterase physostigmine (35 μg/kg, sc) and LVP (0.003 μg/kg, sc), which had no effect on retention when administered alone, produced a synergistic interaction when given together following training. The influence of LVP (0.03 μg/kg, sc) on retention was prevented not only by AAVP (0.01 μg/kg, sc) but also by mecamylamine (5 mg/kg, sc), whereas the effects of nicotine (10.0 μg/kg, sc) were prevented only by mecamylamine. These results suggest that the enhancement of retention induced by vasopressin is probably due to an activation of central nicotinic cholinergic mechanisms which are critical for memory formation.