DENERVATION HYPERSENSITIVITY OF HISTAMINE-H1-RECEPTORS IN RAT-BRAIN CORTEX

WE have studied the effects of the unilateral electrolytic lesion of the medial forebrain bundle at the level of the lateral hypothalamus on the density and functionality of histamine H-1 receptors in rat brain cortex. The treatment resulted, after two and four weeks, in an increase in the maximal phosphoinositide breakdown induced by histamine, which can be accounted for by the appearance of a higher potency component for the response. On the other hand, the density of cortical histamine H-1 receptors, determined by the specific binding of [H-3]mepyramine to membranes, remained unchanged two weeks after the lesion but after four weeks a small but significant increase was also found. These results suggest that the denervation hypersensitivity developed may initially be the result of a more efficient coupling of the H-1 receptors to the effector system prior to the subsequent increase in receptor numbers.