Differential role of histamine in mediating stress-induced changes in central dopaminergic neuronal activity in the rat.

The role of histamine in mediating restraint stress-induced alterations in dopaminergic neuronal activity and alpha-melanocyte-stimulating hormone (alpha MSH) secretion was evaluated in male rats. Dopaminergic neuronal activity was estimated by measuring concentrations of the dopamine metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) in brain regions containing terminals of these neurons. Physical restraint increased DOPAC concentrations in nucleus accumbens and decreased DOPAC concentrations in the intermediate lobe of the pituitary, but was without effect on DOPAC concentrations in either the striatum or median eminence. These data indicate that restraint stress increases mesolimbic, decreases periventricular-hypophysial, and is without effect on nigrostriatal or tuberoinfundibular dopaminergic neuronal activity. Neither depletion of neuronal histamine by alpha-fluoromethylhistidine, blockade of H1 receptors by mepyramine, nor blockade of H2 receptors by zolantidine prevented the stress-induced increase in DOPAC concentrations in the nucleus accumbens suggesting that histaminergic neurons are not major contributors to stress-induced increases in mesolimbic dopaminergic neuronal activity. In contrast, alpha-fluoromethylhistidine- and mepyramine-, but not zolantidine-treatment prevented the stress-induced decrease in DOPAC concentrations in the intermediate lobe. Restraint stress increased alpha MSH secretion; this increase was not prevented by alpha-fluoromethylhistidine, mepyramine, or zolantidine. These data indicate that histaminergic neurons mediate the stress-induced decrease in periventricular-hypophysial dopaminergic neuronal activity through an action at H1 receptors, but do not effect stress-induced alpha MSH secretion.