Rewarding and aversive effects of ethanol: interplay of GABA, glutamate and dopamine.
Ethanol (EtOH) administration is considered to elicit its reinforcing properties by stimulating dopaminergic (DA) transmission in the mesolimbic system. Accordingly, (EtOH) activates dopamine neuronal firing in the Ventro-Tegmental Area (VTA) and DA output in the nucleus accumbens. Concomitantly, EtOH reduces the firing rate of Pars Reticulata (PR) neurons which are thought to exert an inhibitory control over DA neurons. Further, chronic ingestion of EtOH produces tolerance to its sedative effects as to the depressant effect on PR neurons but no tolerance to the DA stimulating action. Moreover the NMDA antagonist MK-801, but not SL-820715, stimulates DA firing, suggesting that this effect is not a general characteristic of NMDA receptor antagonists and questioning the possibility that NMDA-receptor blockade may underlie EtOh-induced activation of DA-ergic transmission. The results indicate that activation of the mesolimbic DA tract is essential in the rewarding properties of EtOH and that neither GABA-ergic inhibition nor NMDA-receptor blockade by EtOH, are causally linked to the EtOH-induced activation of DA-ergic transmission.
Diana
M
M
B.B. Brodie Dept of Neuroscience, University of Cagliari, Italy.
Rossetti
Z L
ZL
Gessa
G
G
D000437:Alcoholism / Q000209:etiology / Q000503:physiopathology / Q000523:psychology; D000818:Animals; D001348:Aversive Therapy; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004298:Dopamine / Q000502:physiology*; D004594:Electrophysiology; D000431:Ethanol / Q000633:toxicity*; D018698:Glutamic Acid / Q000502:physiology*; D008032:Limbic System / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D012201:Reward; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; D000431:Ethanol; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D016291:Dizocilpine Maleate; D004298:Dopamine; C058083:eliprodil