Synergy of Somatostatin – substance P Receptors Antagonists in the Initiation of Catalepsy in Rats

The parkinsonian brain undergoes a decrease in levels of somatostatin (SST) and substance P (SP). According to previous studies, brain SST deficit in rats simulated by i.c.v. injections of SST receptor antagonist, cyclosomatostatin (cSST), increases the speed of catalepsy development. Nevertheless, it is not clear how the SP, a natural ligand of neurokinin-1 (NK1) receptors, contributes to the growth of catalepsy. The present study aimed to find out whether simultaneous blockade of central somatostatin and NK1 receptors can lead to catalepsy, a model for parkinsonian bradykinesia and rigidity. The experiments were conducted on Wistar rats. The blockade of somatostatin and NK1 receptors was simulated by intracerebroventricular injections of cSST and substance L-733,060, respectively. Bar test was used to evaluate the catalepsy. No catalepsy was induced by cSST at 1.0 µg and L-733,060 at 10.0 ng injected separately. Nevertheless, co-administration of these agents led to a clear cataleptic response. Cataleptogenic action of the combination was reversed by SP. These results show that cSST and L-733,060 can synergistically induce catalepsy in the rat. According to these findings, Parkinson’s disease-associated brain deficit in SST and SP could be relevant for pathogenesis of extrapyramidal dysfunctions. Considering the aforementioned findings, the processes mediated by central SST and NK1 receptors could be possible therapeutic targets for parkinsonism.