HISTAMINE INHIBITS DOPAMINE RELEASE IN THE MOUSE STRIATUM VIA PRESYNAPTIC-H3 RECEPTORS

In superfused mouse striatal slices preincubated with [H-3]dopamine 25 nmol/l, the electrically (3 Hz) evoked tritium overflow was inhibited by histamine 10 mumol/l by 18%. The degree of inhibition was increased to 38% by haloperidol but not affected by (1) atropine, (2) reducing the stimulation frequency to 0.3 Hz or (3) increasing the concentration of [H-3]dopamine (used for preincubation) to 100 nmol/l. The effect of histamine was mimicked by the H-3 agonist R-(-)-alpha-methylhistamine; it was not affected by the H-1 antagonist dimetindene and the H-2 antagonist ranitidine but abolished by the H-3 antagonist thioperamide. Tritium overflow evoked by Ca2+ ions (introduced into Ca2+-free, K+-rich medium containing tetrodotoxin) was not affected by histamine 10 mumol/l in the absence, but inhibited (by 30%) in the presence of haloperidol; the effect of histamine was abolished by thioperamide. In conclusion, the dopaminergic nerve terminals in the mouse striatum are endowed with presynaptic H-3 receptors. Simultaneous blockade of dopamine autoreceptors increases the extent of the H-3 receptor-mediated inhibition of dopamine release.