Assessment of the multiple discriminative stimulus effects of ethanol using an ethanol-pentobarbital-water discrimination in rats.
Previous drug discrimination studies have elucidated the importance of gamma-aminobutyric acidA (GABAA), N-methyl-D-aspartate (NMDA) glutamate, and serotonin (5-HT) receptor systems in mediating the discriminative stimulus effects of ethanol. The present study used a three-choice operant drug discrimination procedure in an attempt to determine if salient GABAergic 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 pentobarbital (10.0 mg/kg; intragastrically (i.g.) from ethanol (2.0 g/kg; i.g.) from water (4.7 ml; i.g.) using food reinforcement. Stimulus substitution tests were conducted following the administration of allopregnanolone (1.0-17.0 mg/kg; intraperitoneally (i.p.)), diazepam (0.1-7.3 mg/kg; i.p.), midazolam (0.0056-17.0 mg/kg; i.p.), dizocilpine (0.01-0.56 mg/kg; i.p.), phencyclidine (1.0-5.6 mg/kg; i.p.), CGS 12066B (3-30 mg/kg; i.p.), RU 24969 (0.1-5.6 mg/kg; i.p.) and morphine (1 or 3.0 mg/kg; i.p.). Within the group, allopregnanolone and midazolam completely substituted (> 80%), and diazepam partly substituted (67%) for the discriminative stimulus effects of pentobarbital. Dizocilpine and phencyclidine partly substituted (58 and 57%, respectively) for ethanol without substantial pentobarbital-appropriate responding. RU 24969, CGS 12066B and morphine did not result in complete substitution for either ethanol or pentobarbital, although RU 24969 resulted in partial (68%) pentobarbital substitution. The ability to train the present three-choice discrimination in rats indicates that the discriminative stimulus effects of 10.0 mg/kg pentobarbital were separable from those of 2.0 g/kg ethanol. The results suggest that the pharmacological effects of ethanol, which can control behavior, may seemingly be modified by training conditions (two-versus three-choice discrimination procedures), to the extent that a receptor system prominently linked to the behavioral activity of ethanol (i.e. GABAA) appears no longer to be involved in the interoceptive effects of the drug.
Bowen
C A
CA
Department of Physiology, Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, NC 27157-1083, USA.
Gatto
G J
GJ
Grant
K A
KA
D000818:Animals; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D003975:Diazepam / Q000494:pharmacology; D004193:Discrimination Learning; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D018757:GABA Modulators / Q000494:pharmacology; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology; D008297:Male; D008874:Midazolam / Q000494:pharmacology; D009020:Morphine / Q000494:pharmacology; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors; D009294:Narcotics / Q000494:pharmacology; D010424:Pentobarbital / Q000494:pharmacology*; D010622:Phencyclidine / Q000494:pharmacology; D011280:Pregnanolone / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D020318:Rats, Long-Evans; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D014867:Water / Q000494:pharmacology*
D002492:Central Nervous System Depressants; D018757:GABA Modulators; D006993:Hypnotics and Sedatives; D007211:Indoles; D009294:Narcotics; D011810:Quinoxalines; D017366:Serotonin Receptor Agonists; D014867:Water; C052561:CGS 12066B; C025145:5-methoxy 3-(1,2,3,6-tetrahydro-4-pyridinyl)1H indole; D000431:Ethanol; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D009020:Morphine; D011280:Pregnanolone; D010424:Pentobarbital; D010622:Phencyclidine; D003975:Diazepam; D008874:Midazolam