Effects of chronic ethanol exposure on GABA receptors and GABAB receptor modulation of 3H-GABA release in the hippocampus.
Chronic ethanol treatment (CET), sufficient for decreasing long-term potentiation (LTP) in rats, also enhances 3H-GABA release from hippocampal slices in these same animals. The mechanism for an increase in GABA release may involve changes in presynaptic receptors. Therefore, we characterized presynaptic autoreceptor modulation of 3H-GABA release in hippocampal slices from control and CET rats. The effects of a GABAB receptor agonist (baclofen) and antagonist [2-hydroxy (OH)-saclofen] were tested for their ability to modulate electrically stimulated 3H-GABA release from superfused hippocampal slices. Baclofen decreased stimulated release in a dose-dependent manner and 2-OH-saclofen increased release consistent with the existence of presynaptic GABAB autoreceptors in hippocampus. The GABAA antagonist bicuculline did not significantly modulate basal or stimulated release. When the effects of baclofen and 2-OH-saclofen were measured in animals 48 hr after withdrawal from CET, presynaptic modulation of release by baclofen and 2-OH-saclofen was decreased. In addition, we examined the density of 3H-baclofen and 3H-bicuculline binding in the hippocampal formation using quantitative autoradiographic techniques. We found that the density of 3H-baclofen binding sites was not affected by CET, whereas the density of 3H-bicuculline binding sites was increased by 28% in ethanol-treated rats. These data may explain how CET increases presynaptic regulation of GABA release from hippocampus that may contribute to the decrease in LTP seen in rats after CET.
Peris
J
J
Department of Pharmacodynamics, University of Florida Brain Institute, Gainesville, USA.
Eppler
B
B
Hu
M
M
Walker
D W
DW
Hunter
B E
BE
Mason
K
K
Anderson
K J
KJ
D000437:Alcoholism / Q000503:physiopathology*; D000818:Animals; D017660:Autoreceptors / Q000187:drug effects / Q000502:physiology; D046508:Culture Techniques; D000431:Ethanol / Q000633:toxicity*; D006624:Hippocampus / Q000187:drug effects* / Q000503:physiopathology; D017774:Long-Term Potentiation / Q000187:drug effects* / Q000502:physiology; D008297:Male; D017729:Presynaptic Terminals / Q000187:drug effects / Q000502:physiology; D051381:Rats; D018079:Receptors, GABA / Q000187:drug effects* / Q000502:physiology; D018080:Receptors, GABA-B / Q000187:drug effects* / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D017660:Autoreceptors; D018079:Receptors, GABA; D018080:Receptors, GABA-B; D000431:Ethanol; D005680:gamma-Aminobutyric Acid