Intraseptal microinjection of adrenocorticotropic hormone1-24 antagonizes pentobarbital-induced narcosis and depression of hippocampal cholinergic activity.

Intracerebroventricular or intraseptal microinjection of adrenocorticotropic hormone1-24 (ACTH1-24) to pentobarbital-anesthetized rats and rabbits produced shortening of the duration of narcosis. This analeptic effect was blocked by atropine, indicating the central cholinergic nature of the response. ACTH1-24 also increased hippocampal sodium-dependent high affinity choline uptake activity that had been depressed by the barbiturate. Naloxone-pretreatment also blocked the analeptic and cholinergic activating properties of ACTH1-24. These results suggest that intraseptal ACTH1-24 produces its analeptic effect by activating a hippocampal cholinergic arousal system.