Abstract
The enhancing effect of TRH on dopamine(DA) release from rat striatal slices was investigated in relation to Ca2+ and cholinergic mechanisms. TRH(10-5 ?? 10-3M) facilitated concentration dependently the uptake of 14C-DA by rat striatal slices, while methamphetamine (10-6 ?? 10-4M) exhibited a considerable inhibitory effect. TRH (10-7 ?? 10-3M) alone did not increase the DA release into the incubation medium, but it clearly enhanced the DA release in the concomitant presence of desipramine (5×10-5M). In the superfusion study, TRH (10-5 ?? 10-3M), methamphetamine (10-6 ?? 10-4M) and KCl (2.5 ?? 5.0×10-2M) enhanced the DA release into the perfusion fluid. The DA releasing effect of TRH was completely blocked by cholinergic blockers (scopolamine, hexamethonium and hemicholinium), Ca2+ chelator(EGTA), Ca2+ antagonist (CoCl2) and Ca2+ influx blocker(D-600) or by the removal of Ca2+ from the medium. The methamphetamine-enhanced DA release, however, was not modified by the above treatments except for a partial decline produced by EGTA coupled with the removal of Ca2+. TRH(10-4M) also facilitated the uptake of 3H-norepinephrine (NE) by rat cerebral cortex slices, but methamphetamine (10-6 ?? 10-4M) exhibited a considerable inhibitory effect. In the superfusion study, TRH (10-5 ?? 10-4M) and methamphetamine (10-7 ?? 10-4M) enhanced the NE release into the perfusion fluid. Therefore, it can be concluded that TRH facilitated the DA release from rat striatal slices by mediating through a cholinergic mechanism and by enhancing the influx of Ca2+.
