Adaptation of the adrenocorticotropic response to chronic intermittent stress was altered by intracerebroventricular infusion of hemicholinium-3.

The role of diencephalic cholinergic neurotransmission in regulating hypothalamic-pituitary-adrenocortical (HPA) axis was investigated by means of administration of hemicholinium-3 (HC-3), a blocker of acetylcholine synthesis, in the third ventricle of hemispherectomized pigeons. Except for an early increase in ACTH and corticosterone levels following injection as a bolus of HC-3 that was ascribed to some stress-like situation, all data indicated that hypothalamic acetylcholine depletion resulted in inhibiting effects on the HPA axis. Twenty-four hours after injection of 6 micrograms of HC-3, the response to acute stress was markedly reduced in both magnitude and duration. Permanent instillation of HC-3 in the third ventricle at the rate of 0.25 microgram/h for 9 days led to lowered basal resting HPA activity and severely affected the development of adaptation to chronic intermittent stress. The anticipatory conditioned, endocrine response did not appear whereas attenuation of the poststress component was amplified. It is suggested that cholinergic mechanisms are involved in modulating the HPA function and particularly the conditioning process that takes place in the course of adaptation of the HPA response to chronic intermittent application of the same stressor.