The behavioural effects of RU 24969, a suggested 5-HT1 receptor agonist in rodents and the effect on the behaviour of treatment with antidepressants.
Some behavioural and biochemical consequences of the administration of RU 24969 (5-methoxy-3(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole), a drug which has been shown to be a potent displacing agent at the 5-HT1 binding site, have been studied in mice and rats. In both species RU 24969 produced a dose-dependent increase in locomotor activity. No head-weaving, head-twitching or reciprocal forepaw treading (behaviour suggested to be 5-HT2 receptor mediated) were seen, nor did the body temperature increase p-Chlorophenylalanine did not alter either the behaviour or its intensity. Pretreatment with both methysergide (10 mg/kg) and metergoline (2.5 mg/kg) enhanced the behavioural response in rats, whilst haloperidol (100 micrograms/kg) inhibited the response. Propranolol caused a small and variable decrease in the increase in locomotion induced by RU 24969 in both mice and rats. The drug RU 24969 (10 mg/kg) inhibited the rate of synthesis of 5-HT in rat brain by about 50%. Pretreatment of rats with desmethylimipramine over a longer term or clenbuterol given acutely, treatments known to enhance the behavioural responses of rats to various other 5-HT agonists, did not alter the RU 24969-induced response. Repeated administration of electroconvulsive shock, however, did produce an enhanced locomotor response to RU 24969. The results obtained are consistent with the view that administration of 5-HT agonists, such as quipazine and 5-methoxy-N,N-dimethyltryptamine, produces behaviour that results from stimulation of both 5-HT1 and 5-HT2 receptor populations.
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D001831:Body Temperature / Q000187:drug effects; D001921:Brain / Q000378:metabolism; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects*; D012701:Serotonin / Q000096:biosynthesis; D012702:Serotonin Antagonists / Q000494:pharmacology
D000928:Antidepressive Agents; D007211:Indoles; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; C025145:5-methoxy 3-(1,2,3,6-tetrahydro-4-pyridinyl)1H indole; D012701:Serotonin; D011433:Propranolol