Serotonergic influence on the potentiation of D-amphetamine and apomorphine-induced rotational behavior by the α2-adrenoceptor antagonist 2-methoxy idazoxan in hemiparkinsonian rats

Abstract

The alpha(2)-adrenoceptor antagonists potentiate both ipsilateral and contralateral rotations induced by amphetamine and apomorphine respectively in hemiparkinsonian rats. The present study investigated the role of serotonergic transmission in this potentiation in unilaterally 6-hydroxydopamine nigral lesioned rats. D-amphetamine (0.5 mg/kg, i.p.) produced ipsilateral rotations, which were decreased by the dopamine receptor antagonist haloperidol (0.2 mg/kg, i.p.) and the alpha(1)-receptor antagonist prazosin (1 mg/kg, i.p.). The selective alpha(2)-antagonist 2-methoxy idazoxan (0.2 mg/kg, i.p.) potentiated the amphetamine-induced ipsilateral rotations, that were attenuated by haloperidol and prazosin. The selective serotonin re-uptake inhibitor citalopram (10 mg/kg, i.p.) and selective serotonin synthesis inhibitor p-chlorophenylalanine (150 mg/kg, i.p., 3 days) decreased and increased the observed potentiation respectively. Apomorphine (0.2 mg/kg, s.c.) produced contralateral rotations, which were decreased by haloperidol but not by prazosin. 2-methoxy idazoxan potentiated these rotations which were attenuated by haloperidol but not by prazosin. Citalopram and p-chlorophenylalanine increased and decreased the observed potentiation respectively. Citalopram and p-chlorophenylalanine had no effect by per se on D-amphetamine and apomorphine-induced rotations. 2-methoxy idazoxan alone increased both ipsilateral and contralateral spontaneous rotations. Taken together, these findings indicate that an increase in noradrenergic tone by 2-methoxy idazoxan potentiates both D-amphetamine-induced ipsilateral and apomorphine induced contralateral rotations. alpha(1)-Antagonism attenuates D-amphetamine induced ipsilateral rotations and its potentiation by 2-methoxy idazoxan but not apomorphine rotations or its potentiation. Increasing and decreasing the serotonergic transmission decreases and increases D-amphetamine potentiation, whereas increases and decreases apomorphine potentiation respectively. The possible mechanisms for these findings are discussed.