TY - JOUR
T1 - Evidence for overshadowing by components of the heterogeneous discriminative stimulus effects of ethanol
AU - Green, Kristen L.
AU - Grant, Kathleen A.
N1 - Funding Information:
This work has been supported by the National Institute on Alcohol Abuse and Alcoholism grant RO1 AA-09346 and Training Grant T32 AA07565. The authors would like to thank Dr Ian Stolerman for his contributory efforts in early discussions of the experimental design and also Drs M.A. Nader and H.H. Samson for their critical comments on the manuscript.
Copyright:
Copyright 2007 Elsevier B.V., All rights reserved.
PY - 1998/10/1
Y1 - 1998/10/1
N2 - The present study used a drug discrimination paradigm to characterize the contribution of separate receptor systems to the stimulus effects of different training doses of ethanol. In a two-lever drug discrimination paradigm two groups of adult male Long-Evans rats (n = 8 per group) were trained to discriminate either 1.0 g/kg ethanol from water or 2.0 g/kg ethanol from water, administered intragastrically (i.g.), 30 min prior to the start of daily sessions in which responding was maintained under a fixed ratio 20 schedule of food presentation. Following training, cumulative dosing substitution tests were conducted with the GABA(A) positive modulator pentobarbital (1-17 mg/kg, i.p.), the uncompetitive NMDA antagonist dizocilpine (0.01,0.3 mg/kg, i.p.) and the 5-HT(1B/2C) agonist m- trifluoromethylphenylpiperazine (TFMPP 0.17-1.7 mg/kg, i.p.). Next, the rats initially trained at 1.0 g/kg ethanol were retrained to discriminate 2.0 g/kg ethanol from water, and the rats initially trained at 1.0 g/kg were retrained to discriminate 2.0 g/kg ethanol from water. Both groups were then re-tested with the same ligands. Regardless of training history, animals currently discriminating 1.0 g/kg were more sensitive to the ethanol-like effects of TFMPP and pentobarbital compared to rats discriminating 2.0 g/kg ethanol. However, no difference in sensitivity to the ethanol-Mike effects of dizocilpine based on ethanol training dose was detected. These results support the view that ethanol is a heterogeneous discriminative stimulus comprised of GABA(A), NMDA and 5-HT(1B/2C) receptor-mediated activity. Furthermore, changes in sensitivity to GABA(A) and 5-HT ligands as a function of training dose could be indicative of overshadowing by other components of ethanol's heterogeneous cue. Finally, it appears that the current profile of ethanol's heterogeneous stimulus effects, rather than an interaction with ethanol training history, determines the substitution pattern of specific receptor ligands.
AB - The present study used a drug discrimination paradigm to characterize the contribution of separate receptor systems to the stimulus effects of different training doses of ethanol. In a two-lever drug discrimination paradigm two groups of adult male Long-Evans rats (n = 8 per group) were trained to discriminate either 1.0 g/kg ethanol from water or 2.0 g/kg ethanol from water, administered intragastrically (i.g.), 30 min prior to the start of daily sessions in which responding was maintained under a fixed ratio 20 schedule of food presentation. Following training, cumulative dosing substitution tests were conducted with the GABA(A) positive modulator pentobarbital (1-17 mg/kg, i.p.), the uncompetitive NMDA antagonist dizocilpine (0.01,0.3 mg/kg, i.p.) and the 5-HT(1B/2C) agonist m- trifluoromethylphenylpiperazine (TFMPP 0.17-1.7 mg/kg, i.p.). Next, the rats initially trained at 1.0 g/kg ethanol were retrained to discriminate 2.0 g/kg ethanol from water, and the rats initially trained at 1.0 g/kg were retrained to discriminate 2.0 g/kg ethanol from water. Both groups were then re-tested with the same ligands. Regardless of training history, animals currently discriminating 1.0 g/kg were more sensitive to the ethanol-like effects of TFMPP and pentobarbital compared to rats discriminating 2.0 g/kg ethanol. However, no difference in sensitivity to the ethanol-Mike effects of dizocilpine based on ethanol training dose was detected. These results support the view that ethanol is a heterogeneous discriminative stimulus comprised of GABA(A), NMDA and 5-HT(1B/2C) receptor-mediated activity. Furthermore, changes in sensitivity to GABA(A) and 5-HT ligands as a function of training dose could be indicative of overshadowing by other components of ethanol's heterogeneous cue. Finally, it appears that the current profile of ethanol's heterogeneous stimulus effects, rather than an interaction with ethanol training history, determines the substitution pattern of specific receptor ligands.
KW - Drug discrimination
KW - Ethanol
KW - Overshadowing
KW - Rats
KW - Training dose
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U2 - 10.1016/S0376-8716(98)00086-6
DO - 10.1016/S0376-8716(98)00086-6
M3 - Article
C2 - 9800144
AN - SCOPUS:0032192345
SN - 0376-8716
VL - 52
SP - 149
EP - 159
JO - Drug and Alcohol Dependence
JF - Drug and Alcohol Dependence
IS - 2
ER -