Histamine H-3 receptors depress synaptic transmission in the corticostriatal pathway

The effect of histamine on the main input to the striatum - the corticostri atal pathway - was studied using electrophysiological techniques in brain s lices from rats and mice. Field potentials (FPs) were recorded in the stria tum following stimulation at the border of the striatum and the cortex. Bat h application of histamine caused a pronounced and long-lasting depression of FPs in rat slices with an IC50 of 1.6 muM and a maximal depression of ar ound 40%. In mouse slices histamine also depressed FPs, but to a lesser ext ent and more transiently. Further experiments in rat slices showed that his tamine H-3 receptors were responsible for this depression since the selecti ve H-3 receptor agonist R-alpha -methylhistamine (1 muM) mimicked the actio n of histamine whilst the selective H-3 receptor antagonist, thioperamide ( 10 muM) blocked the depression caused by histamine application. The histami nergic depression was probably not mediated indirectly through interneurons since blockade of GABA(A), GABA(B), nicotinic and muscarinic receptors or nitric oxide synthase did not prevent the histamine effect. Intracellular r ecordings from medium spiny neurons in the striatum revealed that histamine did not affect postsynaptic membrane properties but increased paired-pulse facilitation of excitatory synaptic responses indicating a presynaptic loc us of action. (C) 2000 Elsevier Science Ltd. All rights reserved.