5-HT2 receptor regulation of extracellular GABA levels in the prefrontal cortex.
Monoamines, including both dopamine and serotonin, synapse onto prefrontal cortical interneurons. Dopamine has been shown to activate these GABAergic interneurons, but there are no direct data on the effects of serotonin on GABA release in the prefrontal cortex. We, therefore, examined the effects of the 5-HT2a/c agonist 1-(2,5-dimethoxy-4-iodophenyl-2-aminopropane (DOI) on extracellular GABA levels in the prefrontal cortex of the rat. Local infusions of DOI dose-dependently increased cortical extracellular GABA levels. In addition, systemic DOI administration resulted in Fos protein expression in glutamic acid decarboxylase67-immunoreactive interneurons of the prefrontal cortex. These data indicate that serotonin, operating through a 5-HT2 receptor, acutely activates GABAergic interneurons in the prefrontal cortex. These data further suggest that there may be convergent regulation of interneurons by dopamine and serotonin in the prefrontal cortex.
Abi-Saab
W M
WM
Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut, USA.
Bubser
M
M
Roth
R H
RH
Deutch
A Y
AY
D000818:Animals; D007150:Immunohistochemistry; D007215:Indophenol / Q000031:analogs & derivatives / Q000494:pharmacology; D007395:Interneurons / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000032:analysis / Q000378:metabolism*
D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; C113896:dimethoxy-4-indophenyl-2-aminopropane; D012701:Serotonin; D007215:Indophenol; D005680:gamma-Aminobutyric Acid