Mechanisms in the control of stress responsiveness

Evidence is given of cooperation between pituitary desensitization to the stimulatory action of corticotropin-releasing hormone (CRH) and glucocorticoid negative feedback in the modulation of the stress responsiveness. With regard to the former, we show that the pituitary becomes unresponsive to repeated CRH administration as soon as 15 min after the first one, while the adrenocortical effect of arginine-vasopressin (AVP) during this period is amplified, suggesting the involvement of AVP in the mechanism that permits repeated pituitary-adrenocortical axis activations. The activation of this axis is blocked by the glucocorticoid negative feedback induced by a previous stress. In fact, after a cold stress (4-6 degrees C for 90 min), the responsiveness to a subsequent psychic stressor (but not to a somatic one) is suppressed. Results after neurotoxic lesion of hippocampal and hypothalamic serotoninergic innervations, would indicate that the neurotransmitter is in some way involved in the accomplishment of this phenomenon.