Apomorphine-induced turning behavior in 6-hydroxydopamine lesioned rats is increased by histidine and decreased by histidine decarboxylase, histamine H1 and H2 receptor antagonists, and an H3 receptor agonist

The role of histamine and its receptors in basal ganglia neurocircuitry was assessed in apomorphine-induced turning behavior. Rats with unilateral 6-hydroxydopamine lesions of the substantia nigra pars compacta and medial forebrain bundle were administered histaminergic agents, and apomorphine-induced turning behavior was tested on Days 7 and 14 post-lesion. Compared with saline-treated rats, histidine (500 mg/kg, i.p.), a precursor of histamine, increased turning behavior (p < 0.05), while α-fluoromethylhistidine (α-FMH, 25 μg, i.c.v.), an irreversible inhibitor of histidine decarboxylase, decreased turning behavior (p < 0.05) but only on Day 14 post-lesion. Both the histamine H1 receptor antagonist pyrilamine (10 and 50 μg, i.c.v.) and the H2 receptor antagonist cimetidine (10 and 50 μg, i.c.v.) significantly decreased turning behavior on Days 7 and 14 post-lesion. The histamine H3 receptor agonist immepip (10 μg, i.c.v.) decreased turning behavior (p < 0.05) on Day 14 post-lesion. The present findings indicate the complex interactions of histamine on basal ganglia function.