5-HT2A receptor antagonists inhibit potassium-stimulated gamma-aminobutyric acid release in rat frontal cortex.
Several drugs selective for the serotonin 5-HT2A receptor were tested for their effects on spontaneous and K(+)-evoked [3H] gamma-aminobutyric acid (GABA) release from slices of rat frontal cortex. Under K+ stimulation, the antagonists ketanserin, spiperone, R-(+)-alpha-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenethyl)]- 4-piperidinemethanol (MDL 100,907) and ritanserin inhibited GABA release by 12-31%. Rats were treated with the serotonin-depleting agent para-chlorophenylalanine and with the serotonergic neurotoxin para-chloroamphetamine. In para-chlorophenylalanine-treated animals, stimulated GABA release in the presence of ketanserin remained depressed. In animals treated with both para-chlorophenylalanine and para-chloroamphetamine, ketanserin or the hallucinogenic agonist (2,5-dimethoxy-4-iodophenyl)-2-aminoethane (2C-I) each appeared to decrease stimulated GABA release but this was not significant. However, when ketanserin and 2C-I were both present in the superfusion buffer an additive inhibitory effect was observed, and GABA release was decreased 30%. These results suggest that serotonin facilitates GABA release in cortex via 5-HT2A receptors and that the functional response of this system is resistant to serotonin depletion.
Cozzi
N V
NV
Department of Pharmacology, School of Pharmacy, University of Wisconsin-Madison 53706, USA.
Nichols
D E
DE
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005625:Frontal Lobe / Q000187:drug effects*; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D011188:Potassium / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016713:Ritanserin / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D012702:Serotonin Antagonists; D016713:Ritanserin; D005680:gamma-Aminobutyric Acid; D007650:Ketanserin; D011188:Potassium