CNS mechanisms of alcohol self-administration.

W. J. McBride, J. M. Murphy, G. J. Gatto, A. D. Levy, K. Yoshimoto, L. Lumeng, T. K. Li

Research output: Contribution to journalArticle

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Abstract

Neurochemical and neuropharmacological studies were undertaken to examine the possible involvement of the ventral tegmental area (VTA) dopamine (DA) system and the dorsal raphe nucleus (DRN) serotonin (5-HT) system in regulating oral alcohol self-administration. In vivo microdialysis studies demonstrated that either i.p. ethanol administration (1.0-2.0 g/kg) or local perfusion with ethanol (100 mM) could enhance the extracellular concentrations of both DA and 5-HT in the nucleus accumbens (ACB). Furthermore, the effects of local perfusion with ethanol on DA release in the ACB could be blocked by co-perfusion with a 5-HT3 antagonist. In the selectively-bred alcohol preferring P line of rats, there appears to be abnormal 5-HT and/or DA systems in certain limbic structures, i.e., ACB, olfactory tubercles (OTU) and medial prefrontal cortex (MPF). This is indicated by (a) lower contents of DA and 5-HT; (b) fewer 5-HT immunostained fibers; (c) lower densities of 5-HT1B, 5-HT2 and D2 receptors; and (d) higher densities of 5-HT1A receptors in the CNS of P rats compared to the alcohol-nonpreferring NP line of rats. Neuropharmacological studies demonstrated that local microinfusion of the D2 antagonist, sulpiride, or, at low doses, the DA releaser, d-amphetamine, could increase alcohol drinking by P rats. Intracranial self-administration (ICSA) studies showed that the P line of rats, but not the NP line, will self-administer 50-150 mg% ethanol directly into the VTA. Overall, these results suggest an innate abnormal functioning of the VTA DA and DRN 5-HT systems may be key factors facilitating the rewarding actions of ethanol in the CNS of P rats.

Original languageEnglish
Pages (from-to)463-467
Number of pages5
JournalAlcohol and alcoholism (Oxford, Oxfordshire). Supplement
Volume2
StatePublished - 1993

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Self Administration
Dopamine
Serotonin
Alcohols
Ethanol
Ventral Tegmental Area
Perfusion
Serotonin 5-HT3 Receptor Antagonists
Sulpiride
Dextroamphetamine
Receptor, Serotonin, 5-HT1A
Microdialysis
Nucleus Accumbens
Prefrontal Cortex
Alcohol Drinking

ASJC Scopus subject areas

  • Medicine(all)

Cite this

McBride, W. J., Murphy, J. M., Gatto, G. J., Levy, A. D., Yoshimoto, K., Lumeng, L., & Li, T. K. (1993). CNS mechanisms of alcohol self-administration. Alcohol and alcoholism (Oxford, Oxfordshire). Supplement, 2, 463-467.

CNS mechanisms of alcohol self-administration. / McBride, W. J.; Murphy, J. M.; Gatto, G. J.; Levy, A. D.; Yoshimoto, K.; Lumeng, L.; Li, T. K.

In: Alcohol and alcoholism (Oxford, Oxfordshire). Supplement, Vol. 2, 1993, p. 463-467.

Research output: Contribution to journalArticle

McBride, WJ, Murphy, JM, Gatto, GJ, Levy, AD, Yoshimoto, K, Lumeng, L & Li, TK 1993, 'CNS mechanisms of alcohol self-administration.', Alcohol and alcoholism (Oxford, Oxfordshire). Supplement, vol. 2, pp. 463-467.
McBride WJ, Murphy JM, Gatto GJ, Levy AD, Yoshimoto K, Lumeng L et al. CNS mechanisms of alcohol self-administration. Alcohol and alcoholism (Oxford, Oxfordshire). Supplement. 1993;2:463-467.
McBride, W. J. ; Murphy, J. M. ; Gatto, G. J. ; Levy, A. D. ; Yoshimoto, K. ; Lumeng, L. ; Li, T. K. / CNS mechanisms of alcohol self-administration. In: Alcohol and alcoholism (Oxford, Oxfordshire). Supplement. 1993 ; Vol. 2. pp. 463-467.
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