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.