Intranigral injection of the H 3 agonist immepip and systemic apomorphine elicit ipsilateral turning behaviour in naive rats, but reduce contralateral turning in hemiparkinsonian rats

Abstract

There is evidence that histamine H 3 receptors co-localise with dopamine D 1 receptors on the terminals of striato-nigral neurones. In this work we studied the effect of the local activation of H 3 receptors present in substantia nigra pars reticulata (SNr) on turning behaviour following apomorphine administration to either naive or hemiparkinsonian rats. In naive rats the intranigral (SNr) injection of the H 3 receptor agonist immepip (3.2 or 32 ng/1 μl) resulted in ipsilateral turning following systemic apomorphine (0.5 mg/kg, subcutaneous). The effect of immepip was related to the dose and prevented by the H 3 antagonist thioperamide (5 mg/kg, intraperitoneal). Conversely, in rats with 6-hydroxydopamine (6-OHDA) lesions to either substantia nigra pars compacta or the medial forebrain bundle (mfb), apomorphine-induced contralateral turning was reduced by intranigral immepip, an effect prevented by systemic thioperamide. Our data show that H 3 receptors present in SNr regulate the synaptic output of the basal ganglia, most likely by reducing GABA release from striato-nigral terminals. These results may be relevant for the understanding of the role of histamine and H 3 receptors in the control of motor behaviour both in normal and pathophysiological conditions, such as Parkinson’s disease in which histaminergic innervation and histamine levels in substantia nigra have been shown to increase.