Chronic administration of cholinergic agents: effects on behavior and calmodulin

Rats were implanted subcutaneously with Alza® pumps and 0.9% saline, physostigmine, or scopolamine were continuously infused for 15 days. Twenty-four hours after removal of the pumps all animals were trained on a single trail passive avoidance task. Twenty-four hours after training they were tested for retention. Following behavioral testing, animals were sacrificed, brain regions dissected, frozen and stored (−20°C) for calmodulin determinations. Animals which had previously received chronic infusions of scopolamine performed significantly better than controls, while those which previously received chronic infusions of physostigmine performed significantly worse during the retention test. No significant differences in calmodulin levels (soluble or particulate) were detected across brain regions or drug groups. These results indicate that continuous chronic infusion of drugs which can facilitate or inhibit CNS cholinergic activity can induce performance changes on a learning task opposite to those resulting following the acute administration of these same drugs.