Psychopharmacology

, Volume 139, Issue 1, pp 95–107

The discriminative stimulus effects of ethanol are mediated by NMDA and GABAA receptors in specific limbic brain regions

Authors

  • C. W. Hodge
    • University of California San Francisco, Department of Neurology/Gallo Center, 1001 Potrero Avenue, Building 1, Room 101, San Francisco, CA 94110, USA
  • Amy A. Cox
    • University of California San Francisco, Department of Neurology/Gallo Center, 1001 Potrero Avenue, Building 1, Room 101, San Francisco, CA 94110, USA
Original Investigation

DOI: 10.1007/s002130050694

Cite this article as:
Hodge, C. & Cox, A. Psychopharmacology (1998) 139: 95. doi:10.1007/s002130050694

Abstract

 This study was conducted to assess the involvement of N-methyl-d-aspartate (NMDA) and γ-aminobutyric acid (GABA) receptor systems, located in specific limbic brain regions, in the discriminative stimulus effects of ethanol. Male Long-Evans rats were trained to discriminate between intraperitoneal (IP) injections of ethanol (1 g/kg) and saline on a two-lever drug discrimination task. The rats were then implanted with bilateral injector guides aimed at the nucleus accumbens core (AcbC), prelimbic cortex (PrLC), hippocampus area CA1 (CA1), or extended amygdala (i.e., at the border of the central and basolateral nuclei). Infusions of the non-competitive NMDA antagonist MK 801 in the AcbC or CA1 resulted in dose-dependent full substitution for IP ethanol. MK 801 infusion in the PrLC or amygdala failed to substitute for ethanol. Injection of the competitive NMDA antagonist CPP in the AcbC also failed to substitute for ethanol. Co-infusion of MK 801 in the hippocampus potentiated the effects of MK 801 in the AcbC, whereas NMDA infusion in the hippocampus attenuated the ability of MK 801 in the AcbC to substitute for ethanol. The direct GABAA agonist muscimol resulted in dose-dependent full substitution for IP ethanol when it was injected into the AcbC or amygdala, but failed to substitute when administered in the PrLC. Co-infusion of MK 801, but not CPP, potentiated the effects of muscimol in the AcbC. These results demonstrate that ethanol’s discriminative stimulus function is mediated centrally by NMDA and GABAA receptors located in specific limbic brain regions. The data also suggest that the discriminative stimulus effects of ethanol are mediated by interactions between ionotropic GABAA and NMDA receptors in the nucleus accumbens, and by interactions among brain regions.

Key words MK-801MuscimolDiscriminative stimulusDrug discriminationEthanolGABAANMDALimbic systemNucleus accumbensHippocampusFrontal cortexAmygdalaRat

Copyright information

© Springer-Verlag Berlin Heidelberg 1998