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Enhancement by TRH of the dopamine(DA) agonist-induced circling behavior and effect of TRH itself on circling behavior were investigated. TRH(2.5--20 mg/kg, i.p.) remarkably enhanced the circling behavior induced by apomorphine or-L-DOPA in the mice lesioned unilaterally in the caudate nucleus by injection of 6-hydroxydopamine (60OHDA) or by tissue aspiration with subsequent reserpinization. TRH also enhanced the apomorphine-induced stereotypy in reserpinized normal mice. The above TRH-enhancing action of the circling behavior was potentiated, suppressed or unaffected by alpha-methyl-para-tyrosine (alpha-MT) or GABA-ergic drugs. In the 6-OHDA lesioned mice treated with TRH, the cyclic AMP formation by DA or apomorphine was clearly enhanced in the triatal slices taken from the lesioned side but not from the intact side. In the rats lesioned unilaterally in the nigrostriatal DA pathway by 6-OHDA, high doses of TRH injected i.p. (100 mg/kg) or into the non-lesioned caudate nucleus (50 micrograms) produced circling toward the lesioned side, which was suppressed by haloperidol or alpha-MT. TRH(10(-5)--10(-3)M) increased the 14C-DA release from the rat striatal slices in vitro. These results suggest that TRH at low doses facilitates the DA postsynaptic transmission in association with an increase of DA-stimulated cyclic AMP formation in the striatum under supersensitization of the DA receptors, and also at high doses enhances the DA neuronal activity by increasing the DA release from the striatal nerve terminals.

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Thyrotropin-releasing hormone (TRH): Enhancement of dopamine dependent circling behavior and its own circling-inducing effect in unilateral striatal lesioned animals