HISTAMINE H-3 RECEPTOR ACTIVATION SELECTIVELY INHIBITS DOPAMINE D-1 RECEPTOR-DEPENDENT [H-3] GABA RELEASE FROM DEPOLARIZATION-STIMULATED SLICES OF RAT SUBSTANTIA-NIGRA PARS RETICULATA

The release of [H-3]GABA from slices of rat substantia nigra pars reti culata induced by increasing extracellular K+ from 6 to 15 mM in the p resence of 10 mu M sulpiride was inhibited by 73 +/- 3% by 1 mu M SCH 23390, consistent with a large component of release dependent upon D-1 receptor activation. The histamine H-3 receptor-selective agonist imm epip (1 mu M) and the non-selective agonist histamine (100 mu M) inhib ited [H-3]GABA release by 78 +/- 2 and 80 +/- 2%, respectively. The in hibition by both agonists was reversed by the H-3 receptor antagonist thioperamide(1 mu M). However, in the presence of 1 mu M SCH 23390 dep olarization-induced release of [H-3]GABA was not significantly decreas ed by 1 mu M immepip. In rats depleted of dopamine by pretreatment wit h reserpine, immepip no longer inhibited control release of [H-3]GABA, but in the presence of 1 mu M SKF 38393, which produced a 7 +/- 1-fol d stimulation of release, immepip reduced the release to a level not s tatistically different from that in the presence of immepip alone. Imm epip(1 mu M) also inhibited the depolarization-induced release of [3H] dopamine from substantia nigra pars reticulata slices, by 38 +/- 3%. T he evidence is consistent with the proposition that activation of hist amine H-3 receptors leads to the selective inhibition of the component of depolarization-induced [H-3]GABA release in substantia nigra pars reticulata slices which is dependent upon D-1 receptor activation. Thi s appears to be largely an action at the terminals of the striatonigra l GABA projection neurons, which may be enhanced by a partial inhibiti on of dendritic [H-3]dopamine release. (C) 1997 IBRO. Published by Els evier Science Ltd.