Psychopharmacology

, Volume 154, Issue 1, pp 13–22 | Cite as

The discriminative stimulus properties of self-administered ethanol are mediated by GABAA and NMDA receptors in rats

  • Clyde W. Hodge
  • Amy A. Cox
  • Alison M. Bratt
  • Rosana Camarini
  • Kimberly Iller
  • Stephen P. Kelley
  • Kristin K. Mehmert
  • Michelle A. Nannini
  • M. Foster Olive
Original Investigation

Abstract.

Rationale: The neurobiological systems that mediate the discriminative stimulus effects of self-administered drugs are largely unknown. The present study examined the discriminative stimulus effects of self-administered ethanol. Methods: Rats were trained to discriminate ethanol (1 g/kg, IP) from saline on a two-lever drug discrimination task with sucrose (10% w/v) reinforcement. Test sessions were conducted with ethanol (0 or 10% v/v) added to the sucrose reinforcement to determine if self-administered ethanol would interact with the discriminative stimulus effects of investigator-administered ethanol, or with the ethanol-like discriminative stimulus effects of the GABAA-positive modulator pentobarbital or the non-competitive NMDA antagonist MK-801. Results: During a saline test session, ethanol (10% v/v) was added to the sucrose reinforcement. Responding by all animals began accurately on the saline-appropriate lever and then switched to the ethanol-appropriate lever after rats self-administered a mean dose of 1.2±0.14 g/kg ethanol. During cumulative self-administration trials, responding initially occurred on the saline lever and then switched to the ethanol-appropriate lever after ethanol (0.68±0.13 g/kg) was self-administered. Investigator-administered MK-801 (0.01–1.0 mg/kg, cumulative IP) and pentobarbital (0.3–10.0 mg/kg, cumulative IP) dose-dependently substituted for ethanol. When ethanol (10% v/v) was added to the sucrose reinforcer, MK-801 and pentobarbital dose-response curves were shifted significantly to the left. Conclusions: Self-administered ethanol substituted for and potentiated the stimulus effects of investigator-administered ethanol, suggesting that the discriminative stimulus effects of self-administered ethanol are similar to those produced by investigator-administered ethanol. Self-administered ethanol enhanced the ethanol-like discriminative stimulus effects of MK-801 and pentobarbital, which suggests that the discriminative stimulus effects of self-administered ethanol are mediated by NMDA and GABAA receptors.

Ethanol GABAA NMDA Rat Self-administration Drug discrimination Investigator-administered 

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Copyright information

© Springer-Verlag 2000

Authors and Affiliations

  • Clyde W. Hodge
    • 1
  • Amy A. Cox
    • 1
  • Alison M. Bratt
    • 1
  • Rosana Camarini
    • 1
  • Kimberly Iller
    • 1
  • Stephen P. Kelley
    • 1
  • Kristin K. Mehmert
    • 1
  • Michelle A. Nannini
    • 1
  • M. Foster Olive
    • 1
  1. 1.Department of Neurology, Ernest Gallo Clinic and Research Center, University of California at San Francisco, 5858 Horton Street, Suite 200, Emeryville, CA 94608, USA

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