Blockade of MK-801 induced ipsiversive turning in 6-OHDA lesioned rats by alpha 1-adrenoceptor antagonists.

ABSTRACT

Previously the ipsiversive turning response elicited by MK-801 in rats with unilateral 6-hydroxydopamine lesions of the substantia nigra has been shown to be reduced by the alpha 1-receptor antagonist, prazosin. In these experiments the effects of additional alpha 1-adrenoceptor antagonists were examined to verify the involvement of alpha 1-adrenoceptors in the elucidation of the ipsiversive turning response elicited by MK-801. Both aceperone and azapetine did significantly reduce the ipsiversive turning evoked by MK-801. In contrast, neither agent produced a statistically significant reduction in the contraversive turning evoked by the direct acting dopamine agonist, apomorphine. In addition, aceperone also produced a weak but dose-related inhibition of amphetamine-induced ipsiversive rotation, whereas azapetine partially reduced amphetamine-induced turning a non-dose related manner. These data suggest alpha 1-adrenoceptors may be partially involved in the ipsiversive turning response caused by MK-801 and to a lesser extent by amphetamine. This theory was further supported by the finding that reduction of endogenous norepinephrine levels, via administration of the dopamine-beta-hydroxylase inhibitor FLA-63, markedly reduced the turning evoked by MK-801 and to a lesser degree that produced by amphetamine.