The administration of baclofen to mice increases 5-HT2-mediated head-twitch behaviour and 5-HT2 receptor number in frontal cortex.
Mice were injected with baclofen (10 mg/kg) and then given baclofen in drinking water (10 mg/kg/day). After 1 day of administration of baclofen the head-twitch response to the precursor 5-hydroxytryptophan (5-HTP) was reduced but the response to the agonist 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) was unaltered. However, after 14 days the head-twitch response to both 5-HTP and 5-MeODMT was enhanced and this enhancement was present for 14 days after drug withdrawal. After 14 days of administration of baclofen the number of 5-HT2 receptor binding sites in frontal cortex (labelled by [3H]-ketanserin) was also elevated. It is suggested that the enhanced 5-HT2 function, following longer-term administration of baclofen is the consequence of the drug inhibiting 5-HT release in vivo, as indicated by the observations after acute administration.
D000818:Animals; D001418:Baclofen / Q000494:pharmacology*; D005625:Frontal Lobe / Q000032:analysis / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects*; D011985:Receptors, Serotonin / Q000032:analysis / Q000187:drug effects*
D011985:Receptors, Serotonin; D001418:Baclofen