A behavioural and biochemical study in rats of 5-hydroxytryptamine receptor agonists and antagonists, with observations on structure-activity requirements for the agonists.
British journal of pharmacology July 1, 1981 A R Green, J E Hall, A R Rees 88 citations
Several drugs that block serotonin (5-HT) receptors were tested for their effects on behaviors in rats induced by increasing serotonin activity. Methysergide, methergoline, methiothepin, and (-)-propranolol inhibited head weaving, forepaw treading, and hind-limb abduction, while cyproheptadine, cinanserin, and mianserin had no effect. At a higher dose, cyproheptadine did inhibit the behaviors. Methiothepin also blocked dopamine-related activity, suggesting its effects involve dopamine antagonism. Depleting serotonin with p-chlorophenylalanine enhanced responses to serotonin agonists. The findings suggest that some drugs fail to block serotonin-induced behaviors because they are weak antagonists, and caution is needed when interpreting serotonin's role in behaviors based on single antagonists.