Tacrine or arecoline mediates reversal of anoxia- or AF64A-induced behavioural disorders in the developing rat

A 25 min anoxia, or an intracerebroventricular bilateral 2 nmol dose of ethylcholine aziridinium (AF-64A), administered postnatally to male rat pups, elicited on further development of these behavioural disorders, which are partly related to central cholinergic hypofunction. These included a hyperkinetic syndrome and inferior performance in the passive avoidance test. The anoxia-lesioned group but not the AF-64-A-lesioned one, showed an inferior performance in the active avoidance test. Administration of tacrine, an inhibitor of cholinesterase, or arecoline, a cholinergic agonist, in the drinking water to the nursing mothers, at an estimated daily dose of 15 and 10 mg/kg, then directly to the juvenile rats after weaning and until the age of 40 days, partly reversed the effects of anoxia or AF-64A, normalizing the level of locomotor activity and improving performance in passive avoidance, but not in active avoidance. These beneficial effects persisted long after discontinuation of administration of either drug, suggesting that stimulation of spared cholinoceptors in brain at development had prompted the recovery of cholinergic function.