On the interaction of drugs with the cholinergic nervous system

Abstract

Phencyclidine[1(1-phenylcylohexyl) piperidine] and cyclohexamine [1(1-phenylcyclohexyl) ethylamine) were used as model psychotropic drugs to study the phenomenon of tolerance in mice. The behavioral effects of these drugs were measured by forced motor activity using the rotarod test. Tolerance develops progressively with chronic treatment at a rate and to a degree that are dose-dependent. The optimal conditions for tolerance induction are s.c. administration with 4-h intervals. The process of tolerance development is expressed in concomitant changes in five indices chosen for its quantification: ED₅₀ values, duration, duration-dose dependency, critical falling time, and body weight. All these changes were found to be totally reversible, with no carry-over between two consecutive tolerance cycles. It was established that cyclohexamine is a better tolerance-inducer than phencylidine, although the nature of the tolerance developed for both drugs is qualitatively similar. The significance of these results with respect to putative biochemical tolerance mechanisms is presented and discussed.