Antagonists of somatostatin and NK1 receptors synergistically induce catalepsy in middle-aged Wistar rats

Abstract

Objectives: A decrease in levels of somatostatin (SST) and substance P (SP) is observed in the parkinsonian brain. Previously, brain SST deficit in rats simulated by i.c.v. injections of SST receptor antagonist, cyclosomatostatin (cSST), was found to promote the development of catalepsy. The role of SP, a natural ligand of neurokinin-1 (NK1) receptors, in the development of catalepsy is currently unclear. Here, we evaluated whether simultaneous blockade of central somatostatin and NK1 receptors is able to initiate catalepsy and affect dopamine turnover in the nigrostriatal area of the brain.\nMaterials and methods: The experiments were carried out on middle-aged Wistar rats. The blockade of somatostatin and NK1 receptors was simulated by intracerebroventricular injections of cSST and substance L-733,060, respectively. Catalepsy was evaluated by the bar test. The levels of dopamine and its metabolites in the dorsal striatum and substantia nigra were measured by using HPLC.\nResults: No catalepsy was induced by cSST at 1.0 µg and L-733,060 at 10.0 ng injected separately. However, co-administration of these agents initiated catalepsy and influenced dopamine metabolism in the nigrostriatal area. Cataleptogenic action of the combination was reversed by SP. \nConclusion: The present findings testify that there is some sort of synergy between cSST and L-733,060 in initiation of catalepsy. In the light of these data, PD-related simultaneous brain deficit in SST and SP might be relevant for pathogenesis of extrapyramidal dysfunctions. Given the presented results, the processes mediated by central SST and NK1 receptors may be potential therapeutic targets for parkinsonism.