Reference : Brain ethanol concentrations and ethanol discrimination in rats : effects of dose and time
Scientific journals : Article
Human health sciences : Psychiatry
Human health sciences : Pharmacy, pharmacology & toxicology
Social & behavioral sciences, psychology : Neurosciences & behavior
http://hdl.handle.net/2268/1460
Brain ethanol concentrations and ethanol discrimination in rats : effects of dose and time
English
Quertemont, Etienne mailto [Université de Liège - ULg > Département des sciences cognitives > Psychologie quantitative >]
Green, Heather L. [Wake Forest University > Department of Physiology and Pharmacology > Center for the Neurobehavioral Study of Alcohol > >]
Grant, Kathleen A. [Wake Forest University > Department of Physiology and Pharmacology > Center for the Neurobehavioral Study of Alcohol > >]
2003
Psychopharmacology
Springer Verlag
168
3
262-270
Yes (verified by ORBi)
International
0033-3158
Berlin
Germany
[en] brain ethanol ; drug discrimination ; microdialysis ; acute tolerance ; nucleus accumbens
[en] Rationale. In drug discrimination procedures, the substitution pattern for ethanol of various receptor ligands is dependent upon ethanol training dose, presumably reflecting functionally different concentrations of ethanol in the brain. The discriminative stimulus effects of ethanol are also time-dependent, although very few studies have investigated the time course of ethanol discriminations. Objectives. The present study investigated the relationship between brain ethanol concentrations (BrEC), as measured by intracranial microdialysis of the nucleus accumbens, and the time course of ethanol discriminative effects. Methods. Two groups of rats were trained to discriminate either 1.0 or 2.0 g/kg ethanol from water following a 30-min post-ethanol interval. Following training, the time course of the discriminative stimulus was assessed using a series of abbreviated testing trials at 20-min intervals for 5 h after the administration of various ethanol doses (0, 0.5, 1.0 and 2.0 g/kg). The rats were then fitted with microdialysis probes and the time course of BrECs were determined under conditions similar to the behavioral assessments. Results. BrECs were significantly above zero at 4 min post-gavage and attained peak concentrations of 16 mmol/l, 24 mmol/l and 42 mmol/l at 9 min, 16 min and 95 min after IG administration of 0.5, 1.0 and 2.0 g/kg ethanol, respectively. BrECs were similar in ethanol-naive and ethanol-trained rats, indicating a lack of pharmacokinetic tolerance under these discrimination procedures. The discriminative stimulus effects of ethanol were dose- and time-dependent, with a threshold concentration of approximately 12 mmol/l achieved at 5 min after 1.0 g/kg ethanol gavage in rats trained to discriminate 1.0 g/kg ethanol. Acute tolerance to the discriminative stimulus effects of ethanol was evident from BrECs 2-5 h post-ethanol gavage. Conclusions. Ethanol given intragastrically results in a rapid increase in BrEC, independent of ethanol exposure history. The discriminative stimulus effects of ethanol trained at 30 min post-gavage reflect a specific range of BrEC, and depend on the training dose. These data suggest that qualitatively different stimulus effects of ethanol reflect both different ranges of BrEC, as well as within dose acute tolerance to the discriminative stimulus effects.
Centre de Neurosciences Cognitives et Comportementales
Fonds de la Recherche Scientifique (Communauté française de Belgique) - F.R.S.-FNRS ; National Institute of Alcohol Abuse and Alcoholism AA11997 and AA09246
Researchers ; Professionals
http://hdl.handle.net/2268/1460
10.1007/s00213-003-1437-7

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