Release and accumulation of neurotransmitters in the rat brain: acute effects of ethanol in vitro and effects of long-term voluntary ethanol intake.
Release from and accumulation in tissue slices of some neurotransmitters under acute ethanol in naive rats and in long-term voluntarily ethanol drinking rats were investigated. Slices of the rat caudatoputamen were prelabeled with [3H]choline and release of [3H]acetylcholine was stimulated through either N-methyl-D-aspartate (NMDA) receptors or strychnine-sensitive glycine receptors. Ethanol in vitro at 2 per thousand, 4 per thousand, and 6 per thousand (34 mM, 68 mM, and 102 mM, respectively) concentration-dependently depressed the maximum effect of the concentration-response curve of NMDA in naive rats. In contrast, voluntary ethanol consumption over months led to a significantly enhanced NMDA receptor response characterized by an increase in the maximum effect of the concentration-response curve. The glycine receptor-mediated release of [3H]acetylcholine, which is inhibited by acute ethanol in a competitive-like fashion, was not changed in animals that ingested ethanol over months. Electrically evoked release of [3H]noradrenaline ([3H]NA) and its presynaptic modulation by morphine through mu-opioid receptors in neocortical slices of the rat, preloaded with [3H]NA, was nearly identical in both ethanol-naive rats and in ethanol drinking rats. The accumulation of [3H]gamma-aminobutyric acid in rat cerebellum tissue was neither affected by acute ethanol in vitro nor after chronic ethanol consumption. In summary, long-term voluntary ethanol intake caused a significant increase in NMDA receptor function in the rat caudatoputamen, but did not result in changes in glycine-evoked [3H]acetylcholine release of electrically evoked [3H]NA release modulated by morphine or cerebellar [3H]gamma-aminobutyric acid accumulation.
Darstein
M
M
Sektion Klinische Neuropharmakologie der Neurologischen Universitätsklinik, Neurozentrum, Freiburg, Germany.
Albrecht
C
C
López-Francos
L
L
Knörle
R
R
Hölter
S M
SM
Spanagel
R
R
Feuerstein
T J
TJ
D000109:Acetylcholine / Q000378:metabolism; D000437:Alcoholism / Q000503:physiopathology*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000503:physiopathology; D002421:Caudate Nucleus / Q000187:drug effects / Q000503:physiopathology; D000431:Ethanol / Q000633:toxicity*; D005998:Glycine / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009020:Morphine / Q000494:pharmacology; D016202:N-Methylaspartate / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism*; D011699:Putamen / Q000187:drug effects / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D018377:Neurotransmitter Agents; D016194:Receptors, N-Methyl-D-Aspartate; D000431:Ethanol; D005680:gamma-Aminobutyric Acid; D016202:N-Methylaspartate; D009020:Morphine; D000109:Acetylcholine; D005998:Glycine