Possible involvement of 5-hydroxytryptamine and cyclic-AMP in tolerance to tremorine analgesia in mice

The phenomenon of tolerance to the analgesic action of tremorine in mice was studied by the hot-plate and tail-clip methods. Reduction in 5-HT levels in brain by parachlorophenylalanine pretreatment decreased the ED₅₀ of tremorine analgesia in tremorine tolerant mice. 5-Hydroxytryptophan, l-Dopa or -methyl-para-tyrosine did not influence the analgesic response to tremorine in tremorine tolerant animals. However, theophylline was found to enhance the tolerance to tremorine analgesia.Brain 5-HT and cAMP are probably involved in tremorine tolerance, whereas neither noradrenaline nor dopamine is involved in the phenomenon.