Modulation of striatal serotonin metabolism by baclofen, a gamma-aminobutyric acidB receptor agonist.

Intraperitoneal (i.p.) administration of racemic baclofen (10-40 mg/kg), a gamma aminobutyric acidB (GABAB) Receptor agonist, increased striatal and hippocampal 5-hydroxytryptophan (5-HTP) accumulation after inhibition of L-aromatic amino acid decarboxylase. The baclofen-induced increment of 5-HTP accumulation in the striatum showed a much greater magnitude and longer duration than that in the hippocampus. In contrast, systemic application of baclofen (10-40 mg/kg, i.p.) failed to modify the rate of serotonin (5-HT) disappearance during inhibition of tryptophan hydroxylase in the striatum and hippocampus. Acute cerebral hemitransection decreased striatal 5-HTP accumulation and completely blocked the ability of baclofen to enhance 5-HT synthesis in the striatum. Furthermore, there were no changes in striatal 5-HTP accumulation after intrastriatal infusion of baclofen and GABA. These findings suggested that systemically applied baclofen facilitates in vivo 5-HT synthesis in the striatum via primarily stimulating GABAB receptors located in the extra-striatal area(s).