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Current Topics in Pharmacology   Volumes    Volume 22 
Cyclosomatostatin-induced catalepsy in the aged rat: a response to levodopa, diphenhydramine and nicotine
Ilya D. Ionov, Irina I. Pushinskaya, Nicholas P. Gorev
Pages: 45 - 54
Number of pages: 10
Current Topics in Pharmacology
Volume 22 

Copyright © 2018 Research Trends. All rights reserved

A decrease in somatostatin level is observed in parkinsonian brain. We recently reported that rats given an intracerebroventricular injection of a somatostatin antagonist, cyclosomatostatin, fall into catalepsy; the effect was observed in aged but not young animals. To evaluate the predictive validity of the cyclosomatostatin-induced catalepsy as a model of extrapyramidal disorders, the sensitivity of this catalepsy to clinically effective anti-parkinsonian agents was determined. We examined the effects of levodopa and histamine antagonists; also, given an inverse association between Parkinson’s disease and tobacco smoking, nicotine was tested. The experiments were conducted using 27-28-month-old male Wistar rats. Catalepsy was measured using the bar test. Cyclosomatostatin-induced catalepsy was strongly antagonized by levodopa, which indicates a role for central dopaminergic deficiency in this model. Similarly, histamine H1-receptor antagonist, diphenhydramine, exhibited anticataleptic activity; in contrast, antagonists at H2- and H3-receptors were without effect. Cataleptic response was inhibited by nicotine; the nicotine sensitivity distinguishes this catalepsy from other models, in particular, from haloperidol-induced catalepsy. Diphenhydramine and nicotine alone only partly suppressed catalepsy; however, co-administration of these drugs almost totally reversed the cataleptogenic effect of cyclosomatostatin. Thus, a similarity between the cyclosomatostatin-induced catalepsy and Parkinson’s disease with regard to the sensitivity to anti-parkinsonian agents was found. This supports the validity of the model as well as the role of somatostatinergic deficiency in the mechanism of parkinsonian symptoms. Co-administration of diphenhydramine and nicotine appears to be a promising treatment for extrapyramidal disorders in Parkinson’s disease.
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