Pharmacological analysis of the heterogeneous discriminative stimulus effects of ethanol in rats using a three-choice ethanol-dizocilpine-water discrimination |
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Authors: | Carrie A. Bowen K. A. Grant |
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Affiliation: | (1) Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1083, USA e-mail: kgrant@cpm.bgsm.edu, Fax: +1-510-716-8501, US;(2) Department of Comparative Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA, US |
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Abstract: | The present study used a three-choice operant drug discrimination procedure to determine if NMDA-mediated discriminative stimulus effects could be separated from other stimulus effects of 2.0 g/kg ethanol. Adult male Long-Evans rats (n = 7) were trained to discriminate dizocilpine (0.17 mg/kg; IG) from ethanol (2.0 g/kg; IG) from water (4.7 ml; IG) using food reinforcement. Substitution tests were conducted following administration of the GABAA positive modulators allopregnanolone (5.6–30.0 mg/kg; IP), diazepam (0.3–10.0 mg/kg; IP) and pentobarbital (1.0–21.0 mg/kg; IP), the non-competitive NMDA antagonist phencyclidine (0.3–10.0 mg/kg; IP), the 5-HT1 agonists TFMPP (0.3–5.6 mg/kg; IP) and RU 24969 (0.3–3.0 mg/kg; IP), and isopropanol (0.10–1.25 g/kg; IP). Allopregnanolone, diazepam and pentobarbital substituted completely (>80%) for ethanol. Isopropanol partially (77%) substituted for ethanol. Phencyclidine substituted completely for dizocilpine. RU 24969 and TFMPP did not completely substitute for either training drug, although RU 24969 partially (62%) substituted for ethanol. Successful training of this three-choice discrimination indicates that the discriminative stimulus effects of 0.17 mg/kg dizocilpine were separable from those of 2.0 g/kg ethanol. The finding that attenuation of NMDA-mediated effects of ethanol occurred without altering significantly GABAA- and 5-HT1-mediated effects suggests that the NMDA component may be independent of other discriminative stimulus effects of 2.0 g/kg ethanol. Received: 18 November 1997 / Final version: 10 February 1998 |
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Keywords: | Ethanol Dizocilpine GABAA 5-HT NMDA Drug discrimination Rat Alcohol |
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