Light stimulates dopamine (DA) turnover in the dark-adapted rat retina. This effect is suppressed by the γ-aminobutyric acid (GABA) agonist, muscimol. A low dosage of muscimol (6.6 μmol/kg i.v. cumulative) exerts no change in DA turnover while higher dosages (13.2 and 26.4 μmol/kg) reduce this response in a dose-dependent fashion. Since barbiturates appear to potentiate GABA function, we tested the effect of several barbiturates on the muscimol-mediated reduction of the light-evoked activation of DA turnover. The decline in retinal DA content after α-methyl-p-tyrosine was used as an indication of turnover. Neither pentorbarbital (160 μmol/kg i.v.) nor the low dosage of muscimol alone significantly altered the light-evoked increase in retinal DA turnover. However, the combination of pentobarbital and muscimol significantly reduced the light-mediated increase in DA turnover to a level below that normally observed in dark-maintained animals. In a previous study, a comparable effect was produced by a 4-fold greater dosage of muscimol alone. The GABA antagonist, picrotoxinin reversed the combined action of these drugs suggesting their inhibitory effect is mediated via a GABA receptor. Phenobarbital (300 or 590 μmol/kg i.v.) also augmented the muscimol-mediated suppression of DA turnover but had no effect alone. Barbital alone at an anesthetic dosage reduced the light-evoked activation of DA turnover without significantly potentiating muscimol. This convulsant barbiturate, 5-(2-cyclohexylidene-ethyl)-5-ethyl barbiturate produced no change in retinal DA turnover either in the presence or absence of muscimol. These results provide evidence for a GABA potentiating component to the anesthetic and anticonvulsant mechanism of barbiturate action and the first neurochemical demonstration of barbiturate-mediated potentiation of a GABA agonist.
|Idioma original||English (US)|
|Número de páginas||5|
|Publicación||Journal of Pharmacology and Experimental Therapeutics|
|Estado||Published - 1980|
ASJC Scopus subject areas
- Molecular Medicine