Histamine H(3) receptors depress synaptic transmission in the corticostriatal pathway.
The effect of histamine on the main input to the striatum - the corticostriatal pathway - was studied using electrophysiological techniques in brain slices from rats and mice. Field potentials (FPs) were recorded in the striatum following stimulation at the border of the striatum and the cortex. Bath application of histamine caused a pronounced and long-lasting depression of FPs in rat slices with an IC(50) of 1.6 microM and a maximal depression of around 40%. In mouse slices histamine also depressed FPs, but to a lesser extent and more transiently. Further experiments in rat slices showed that histamine H(3) receptors were responsible for this depression since the selective H(3) receptor agonist R-alpha-methylhistamine (1 microM) mimicked the action of histamine whilst the selective H(3) receptor antagonist, thioperamide (10 microM) blocked the depression caused by histamine application. The histaminergic 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 recordings 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 locus of action.
Doreulee
N
N
Department of Physiology II, Heinrich-Heine-University, POB 101007, D-40001, Düsseldorf, Germany.
Yanovsky
Y
Y
Flagmeyer
I
I
Stevens
D R
DR
Haas
H L
HL
Brown
R E
RE
D000818:Animals; D001369:Axons / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects*; D004567:Electrodes, Implanted; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D007395:Interneurons / Q000187:drug effects; D008297:Male; D051379:Mice; D017072:Neostriatum / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D017470:Receptors, Glutamate / Q000187:drug effects; D018100:Receptors, Histamine H3 / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects*
D017470:Receptors, Glutamate; D018100:Receptors, Histamine H3; D006632:Histamine