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.