Increased behavioural response to 5-methoxy-N,N-dimethyltryptamine but not to RU-24969 after intraventricular 5,7-dihydroxytryptamine administration.

Destroying serotonin-producing neurons in the brain with a chemical (5,7-DHT) made rats more sensitive to a drug that activates serotonin receptors (5-MeO-DMT). The stronger behavioral response matched how much serotonin was lost. But the same treatment did not increase the hyperactivity caused by a different drug (RU-24969) that targets a specific serotonin receptor subtype (5HT1). This suggests that different serotonin receptors control different behaviors and that losing serotonin neurons changes sensitivity to some, but not all, receptor-activating drugs.

Study at a glance

Abstract

Chemical lesioning of the 5-hydroxytryptamine neurones in the brain with 5,7-dihydroxytryptamine (200 micrograms i.c.v., 14 or 21 days previously) resulted in an enhanced behavioral response following administration of the 5-hydroxytryptamine receptor agonist 5-methoxy-N,N-dimethyltryptamine (2.5 mg/kg). The increase in the behavioural response showed a positive correlation with the decrease in whole brain 5-hydroxytryptamine levels. In contrast, there was no increase in the hyperlocomotion produced by the 5HT1 receptor agonist RU-24969 (3.5 mg/kg). The results are discussed in relation to the proposed 5-hydroxytryptamine receptor subtypes.