Effects of acute and chronic ethanol treatment on pre- and postsynaptic responses to baclofen in rat hippocampus.
Interactions between the GABAB receptor and acute or chronic ethanol treatment were studied using extracellular and intracellular electrophysiological recording techniques. Bath application of the GABAB receptor agonist, (-)-baclofen (0.1-100 microM) induced concentration-dependent inhibition of extracellularly recorded dendritic excitatory postsynaptic potentials (EPSPs) in the CA1 region of hippocampal slices. Responses to baclofen were unchanged relative to control either by simultaneous application of ethanol (10-60 mM) or by previous chronic ethanol exposure. The membrane potential of CA1 pyramidal neurons was reversibly hyperpolarized an average of 5 mV by pressure ejection of baclofen (1 mM). Bath application of ethanol (30 mM) alone occasionally caused a small depolarization of resting membrane potentials in CA1 neurons but failed to increase hyperpolarizing responses to pressure-ejected baclofen. However, in slices from chronic ethanol-treated animals hyperpolarizing responses to bath-applied baclofen (10 microM) were reduced by approximately 30% relative to controls. These results suggest that GABAB-mediated responses in CA1 hippocampal pyramidal neurons are relatively resistant to the acute effects of ethanol, but that continuous exposure to ethanol sufficient to induce physical dependence may evoke an adaptive reduction in some GABAB receptor mediated responses.
Frye
G D
GD
Department of Medical Pharmacology and Toxicology, Texas A&M University, College of Medicine, College Station 77843-1114.
Taylor
L
L
Trzeciakowski
J P
JP
Griffith
W H
WH
D000818:Animals; D001418:Baclofen / Q000494:pharmacology*; D004594:Electrophysiology; D000431:Ethanol / Q000494:pharmacology*; D005110:Extracellular Space / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D007425:Intracellular Membranes / Q000502:physiology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013569:Synapses / Q000187:drug effects*; D013997:Time Factors
D000431:Ethanol; D001418:Baclofen