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).
Nishikawa
T
T
Division of Mental Disorder Research, National Institute of Neuroscience, NCNP, Tokyo, Japan.
Scatton
B
B
Enomoto
T
T
Shinohara
K
K
Takahashi
K
K
D000818:Animals; D001418:Baclofen / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000145:classification / Q000187:drug effects* / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D011963:Receptors, GABA-A; D012701:Serotonin; D005680:gamma-Aminobutyric Acid; D001418:Baclofen