Evidence for overshadowing by components of the heterogeneous discriminative stimulus effects of ethanol

Kristen L. Green, Kathleen (Kathy) Grant

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)149-159
Number of pages11
JournalDrug and Alcohol Dependence
Volume52
Issue number2
DOIs
StatePublished - Oct 1 1998
Externally publishedYes

Fingerprint

stimulus
Ethanol
evidence
water
substitution
discrimination
Rats
paradigm
drug
gamma-Aminobutyric Acid
Group
history
Dizocilpine Maleate
Water
Pentobarbital
N-Methylaspartate
Ligands
animal
Serotonin
food

Keywords

  • Drug discrimination
  • Ethanol
  • Overshadowing
  • Rats
  • Training dose

ASJC Scopus subject areas

  • Medicine(all)
  • Behavioral Neuroscience
  • Toxicology
  • Health(social science)

Cite this

Evidence for overshadowing by components of the heterogeneous discriminative stimulus effects of ethanol. / Green, Kristen L.; Grant, Kathleen (Kathy).

In: Drug and Alcohol Dependence, Vol. 52, No. 2, 01.10.1998, p. 149-159.

Research output: Contribution to journalArticle

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