Serotonin, dopamine and GABA involvement in alcohol drinking of selectively bred rats

W. J. McBride, J. M. Murphy, L. Lumeng, T. K. Li

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Neurochemical and neuropharmacological studies were undertaken to assess the involvement of CNS serotonin (5-HT), dopamine (DA) and GABA systems in regulating the alcohol-drinking behavior of two lines of rats selectively bred for their high alcohol-seeking behavior, namely the alcohol-preferring P line and the high alcohol-drinking HAD line of rats. Neurochemical data indicate that high alcohol-seeking behavior (when compared with data from rats with low alcohol-seeking characteristics) is associated with: a) lower (10-20%; p < 0.05) contents of 5-HT in certain limbic regions (e.g., nucleus accumbens, frontal cortex, hypothalamus and hippocampus); b) a lower (10-15%; p < 0.05) content of DA in the nucleus accumbens; c) higher (20-35%; p < 0.05) densities of 5-HT1A binding sites in some limbic regions (e.g., medial nucleus accumbens, medial prefrontal cortex and ventral hippocampus); and d) a greater (20-50%) density of GABA axon terminals in the nucleus accumbens. Furthermore, the acute administration of high doses of ethanol appears to increase the activity of the 5-HT and DA projections to the nucleus accumbens of the P line of rats (as indicated by the 20-30% elevated tissue levels of 5-HT and DA metabolites following IP ethanol administration); neuronal tolerance to alcohol appears to develop in both these monoamine pathways, as suggested by an attenuated effect on metabolite levels by a challenge dose of ethanol given to P rats that had been chronically drinking alcohol. The IP administration of agents which can increase the physiologically active pool of 5-HT (e.g., fluoxetine, an uptake inhibitor; fenfluramine, a releaser; and D,L-5-hydroxytryptophan, an immediate precursor) or which can mimic 5-HT (e.g., 5-HT1 and 5-HT2 agonists) all significantly deceased the volitional alcohol intake of the high alcohol-seeking rats. Similarly, the IP administration of a DA uptake inhibitor, DA releaser or D2 agonist also reduced the volitional oral intake of alcohol by the P line of rats. In addition, the consumption of alcohol by the P line of rats is reduced by IP administration of Ro 15-4513, an inverse agonist at the GABAA-benzodiazepine-Cl- receptor complex. Overall, the data suggest that abnormalities exist in certain 5-HT, DA and GABA systems in the CNS of P and HAD rats and that these abnormal transmitter systems may be major underlying biological factors contributing to their high alcohol-seeking characteristics. A hypothesis is offered to explain the involvement of the 5-HT, DA and GABA systems of the nucleus accumbens in regulating alcohol drinking of the selectively bred P and HAD lines of rats.

Original languageEnglish
Pages (from-to)193-202
Number of pages10
JournalAnnual Review of Addictions Research and Treatment
Volume2
Issue numberC
StatePublished - 1992

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Alcohol Drinking
gamma-Aminobutyric Acid
Dopamine
Serotonin
Alcohols
Nucleus Accumbens
Ethanol
Hippocampus
Dopamine Uptake Inhibitors
Serotonin 5-HT2 Receptor Agonists
Fenfluramine
5-Hydroxytryptophan
Drinking Behavior
Fluoxetine
Presynaptic Terminals
Biological Factors
Frontal Lobe
GABA-A Receptors
Prefrontal Cortex
Hypothalamus

Keywords

  • (±)-8-Hydroxy-2-(di-N-propylamino)tetralin (8-OH DPAT)
  • (±)1-(2
  • 1-[3-(Trifluoromethyl)phenyl]-piperazine (TFMPP)
  • 5-Dimethoxy-4-iodophenyl)-2-aminopropane (DOI)
  • Alcohol-drinking behavior
  • Alcohol-preferring rats
  • Bromocryptine
  • Dopamine and alcohol drinking
  • Fluoxetine
  • GABA and alcohol drinking
  • GBR 12909
  • Ro 15-4513
  • Serotonin and alcohol drinking

ASJC Scopus subject areas

  • Medicine (miscellaneous)

Cite this

Serotonin, dopamine and GABA involvement in alcohol drinking of selectively bred rats. / McBride, W. J.; Murphy, J. M.; Lumeng, L.; Li, T. K.

In: Annual Review of Addictions Research and Treatment, Vol. 2, No. C, 1992, p. 193-202.

Research output: Contribution to journalArticle

McBride, W. J. ; Murphy, J. M. ; Lumeng, L. ; Li, T. K. / Serotonin, dopamine and GABA involvement in alcohol drinking of selectively bred rats. In: Annual Review of Addictions Research and Treatment. 1992 ; Vol. 2, No. C. pp. 193-202.
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AU - McBride, W. J.

AU - Murphy, J. M.

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AU - Li, T. K.

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N2 - Neurochemical and neuropharmacological studies were undertaken to assess the involvement of CNS serotonin (5-HT), dopamine (DA) and GABA systems in regulating the alcohol-drinking behavior of two lines of rats selectively bred for their high alcohol-seeking behavior, namely the alcohol-preferring P line and the high alcohol-drinking HAD line of rats. Neurochemical data indicate that high alcohol-seeking behavior (when compared with data from rats with low alcohol-seeking characteristics) is associated with: a) lower (10-20%; p < 0.05) contents of 5-HT in certain limbic regions (e.g., nucleus accumbens, frontal cortex, hypothalamus and hippocampus); b) a lower (10-15%; p < 0.05) content of DA in the nucleus accumbens; c) higher (20-35%; p < 0.05) densities of 5-HT1A binding sites in some limbic regions (e.g., medial nucleus accumbens, medial prefrontal cortex and ventral hippocampus); and d) a greater (20-50%) density of GABA axon terminals in the nucleus accumbens. Furthermore, the acute administration of high doses of ethanol appears to increase the activity of the 5-HT and DA projections to the nucleus accumbens of the P line of rats (as indicated by the 20-30% elevated tissue levels of 5-HT and DA metabolites following IP ethanol administration); neuronal tolerance to alcohol appears to develop in both these monoamine pathways, as suggested by an attenuated effect on metabolite levels by a challenge dose of ethanol given to P rats that had been chronically drinking alcohol. The IP administration of agents which can increase the physiologically active pool of 5-HT (e.g., fluoxetine, an uptake inhibitor; fenfluramine, a releaser; and D,L-5-hydroxytryptophan, an immediate precursor) or which can mimic 5-HT (e.g., 5-HT1 and 5-HT2 agonists) all significantly deceased the volitional alcohol intake of the high alcohol-seeking rats. Similarly, the IP administration of a DA uptake inhibitor, DA releaser or D2 agonist also reduced the volitional oral intake of alcohol by the P line of rats. In addition, the consumption of alcohol by the P line of rats is reduced by IP administration of Ro 15-4513, an inverse agonist at the GABAA-benzodiazepine-Cl- receptor complex. Overall, the data suggest that abnormalities exist in certain 5-HT, DA and GABA systems in the CNS of P and HAD rats and that these abnormal transmitter systems may be major underlying biological factors contributing to their high alcohol-seeking characteristics. A hypothesis is offered to explain the involvement of the 5-HT, DA and GABA systems of the nucleus accumbens in regulating alcohol drinking of the selectively bred P and HAD lines of rats.

AB - Neurochemical and neuropharmacological studies were undertaken to assess the involvement of CNS serotonin (5-HT), dopamine (DA) and GABA systems in regulating the alcohol-drinking behavior of two lines of rats selectively bred for their high alcohol-seeking behavior, namely the alcohol-preferring P line and the high alcohol-drinking HAD line of rats. Neurochemical data indicate that high alcohol-seeking behavior (when compared with data from rats with low alcohol-seeking characteristics) is associated with: a) lower (10-20%; p < 0.05) contents of 5-HT in certain limbic regions (e.g., nucleus accumbens, frontal cortex, hypothalamus and hippocampus); b) a lower (10-15%; p < 0.05) content of DA in the nucleus accumbens; c) higher (20-35%; p < 0.05) densities of 5-HT1A binding sites in some limbic regions (e.g., medial nucleus accumbens, medial prefrontal cortex and ventral hippocampus); and d) a greater (20-50%) density of GABA axon terminals in the nucleus accumbens. Furthermore, the acute administration of high doses of ethanol appears to increase the activity of the 5-HT and DA projections to the nucleus accumbens of the P line of rats (as indicated by the 20-30% elevated tissue levels of 5-HT and DA metabolites following IP ethanol administration); neuronal tolerance to alcohol appears to develop in both these monoamine pathways, as suggested by an attenuated effect on metabolite levels by a challenge dose of ethanol given to P rats that had been chronically drinking alcohol. The IP administration of agents which can increase the physiologically active pool of 5-HT (e.g., fluoxetine, an uptake inhibitor; fenfluramine, a releaser; and D,L-5-hydroxytryptophan, an immediate precursor) or which can mimic 5-HT (e.g., 5-HT1 and 5-HT2 agonists) all significantly deceased the volitional alcohol intake of the high alcohol-seeking rats. Similarly, the IP administration of a DA uptake inhibitor, DA releaser or D2 agonist also reduced the volitional oral intake of alcohol by the P line of rats. In addition, the consumption of alcohol by the P line of rats is reduced by IP administration of Ro 15-4513, an inverse agonist at the GABAA-benzodiazepine-Cl- receptor complex. Overall, the data suggest that abnormalities exist in certain 5-HT, DA and GABA systems in the CNS of P and HAD rats and that these abnormal transmitter systems may be major underlying biological factors contributing to their high alcohol-seeking characteristics. A hypothesis is offered to explain the involvement of the 5-HT, DA and GABA systems of the nucleus accumbens in regulating alcohol drinking of the selectively bred P and HAD lines of rats.

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KW - Alcohol-drinking behavior

KW - Alcohol-preferring rats

KW - Bromocryptine

KW - Dopamine and alcohol drinking

KW - Fluoxetine

KW - GABA and alcohol drinking

KW - GBR 12909

KW - Ro 15-4513

KW - Serotonin and alcohol drinking

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