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

C. W. Hodge, A. A. Cox, A. M. Bratt, R. Camarini, K. Iller, S. P. Kelley, K. K. Mehmert, M. A. Nannini, Michael Olive

Research output: Contribution to journalArticle

32 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)13-22
Number of pages10
JournalPsychopharmacology
Volume154
Issue number1
DOIs
StatePublished - 2001
Externally publishedYes

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GABA-A Receptors
N-Methyl-D-Aspartate Receptors
Ethanol
Dizocilpine Maleate
Pentobarbital
Sucrose
Research Personnel
Self Administration
N-Methylaspartate

Keywords

  • Drug discrimination
  • Ethanol
  • GABA
  • Investigator-administered
  • NMDA
  • Rat
  • Self-administration

ASJC Scopus subject areas

  • Pharmacology

Cite this

The discriminative stimulus properties of self-administered ethanol are mediated by GABAA and NMDA receptors in rats. / Hodge, C. W.; Cox, A. A.; Bratt, A. M.; Camarini, R.; Iller, K.; Kelley, S. P.; Mehmert, K. K.; Nannini, M. A.; Olive, Michael.

In: Psychopharmacology, Vol. 154, No. 1, 2001, p. 13-22.

Research output: Contribution to journalArticle

Hodge, CW, Cox, AA, Bratt, AM, Camarini, R, Iller, K, Kelley, SP, Mehmert, KK, Nannini, MA & Olive, M 2001, 'The discriminative stimulus properties of self-administered ethanol are mediated by GABAA and NMDA receptors in rats', Psychopharmacology, vol. 154, no. 1, pp. 13-22. https://doi.org/10.1007/s002130000619
Hodge, C. W. ; Cox, A. A. ; Bratt, A. M. ; Camarini, R. ; Iller, K. ; Kelley, S. P. ; Mehmert, K. K. ; Nannini, M. A. ; Olive, Michael. / The discriminative stimulus properties of self-administered ethanol are mediated by GABAA and NMDA receptors in rats. In: Psychopharmacology. 2001 ; Vol. 154, No. 1. pp. 13-22.
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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.",
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AU - Hodge, C. W.

AU - Cox, A. A.

AU - Bratt, A. M.

AU - Camarini, R.

AU - Iller, K.

AU - Kelley, S. P.

AU - Mehmert, K. K.

AU - Nannini, M. A.

AU - Olive, Michael

PY - 2001

Y1 - 2001

N2 - 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.

AB - 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.

KW - Drug discrimination

KW - Ethanol

KW - GABA

KW - Investigator-administered

KW - NMDA

KW - Rat

KW - Self-administration

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