5-HT sub(2A) receptor antagonists inhibit potassium-stimulated gamma -aminobutyric acid release in rat frontal cortex

• Published in: European journal of pharmacology 1996-08, Vol.309 (1), p.25-31
• Main Authors: Cozzi, N V, Nichols, DE
• Format: Article
• Language: English
• ISSN: 0014-2999

Several drugs selective for the serotonin 5-HT sub(2A) receptor were tested for their effects on spontaneous and K super(+)-evoked [ super(3)H] gamma -amino-butyric acid (GABA) release from slices of rat frontal cortex. Under K super(+) 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-di-methoxy-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-HT sub(2A) receptors and that the functional response of this system is resistant to serotonin depletion.