PHARMACOLOGICAL ANALYSIS OF THE HETEROGENEOUS DISCRIMINATIVE STIMULUSEFFECTS OF ETHANOL IN RATS USING A 3-CHOICE ETHANOL-DIZOCILPINE-WATERDISCRIMINATION
Ca. Bowen et Ka. Grant, PHARMACOLOGICAL ANALYSIS OF THE HETEROGENEOUS DISCRIMINATIVE STIMULUSEFFECTS OF ETHANOL IN RATS USING A 3-CHOICE ETHANOL-DIZOCILPINE-WATERDISCRIMINATION, Psychopharmacology, 139(1-2), 1998, pp. 86-94
The present study used a three-choice operant drug discrimination proc
edure to determine if NMDA-mediated discriminative stimulus effects co
uld be separated from other stimulus effects of 2.0 g/kg ethanol. Adul
t male Long-Evans rats (n = 7) were trained to discriminate dizocilpin
e (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 GABA(A) 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). A
llopregnanolone, diazepam and pentobarbital substituted completely (>8
0%) for ethanol. Isopropanol partially (77%) substituted for ethanol.
Phencyclidine substituted completely for dizocilpine. RU 24969 and TFM
PP 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 st
imulus effects of 0.17 mg/kg dizocilpine were separable from those of
2.0 g/kg ethanol. The finding that attenuation of NMDA-mediated effect
s of ethanol occurred without altering significantly GABA(A)- and 5-HT
1-mediated effects suggests that the NMDA component may be independent
of other discriminative stimulus effects of 2.0 g/kg ethanol.