Serotonin mechanisms in alcohol drinking behavior

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

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

Rat lines selectively bred for disparate alcohol-drinking behaviors exhibit innate differences in the contents of serotonin (5-HT) in several CNS limbic regions, e.g., nucleus accumbens (ACB), frontal cortex, hypothalamus, and olfactory tubercles. In these regions, the selectively bred alcohol-preferring (P) line has levels approximately 20% (P < 0.05) lower than values obtained for the alcohol-nonpreferring (NP) line. In addition, in some limbic regions, the densities of (1) 5-HT1(A) receptors are higher by approximately 30% and (2) 5-HT(1B) and 5-HT2 receptors are lower (by 25-40%) in the P than in the NP line. Systemic administration of agents that increase synaptic levels of 5-HT, such as fluoxetine (a 5-HT uptake inhibitor), d-fenfluramine (a 5-HT releaser) and D, E-5-hydroxytryptophan (an immediate precursor of 5-HT), significantly decreased alcohol consumption of the P line of rats. Systemic (1.0 and 2.0 g/kg ip) administration or local perfusion (100 mM) of ethanol significantly increased the extracellular levels of 5-HT in the ACB of unselected Wistar rats. An interaction of the dorsal raphe nucleus (DRN) 5-HT system with the ventral tegmental area (VTA) dopamine (DA) pathway projecting to the ACB was indicated by the findings that DA release in the ACB increased and decreased following stimulation and inhibition, respectively, of DRN 5-HT neurons. Moreover, an involvement of 5-HT in mediating alcohol-stimulated DA release in the ACB is indicated by the observation that local application of a 5-HT3 antagonist can attenuate this stimulated release. Overall, the data suggest that an innate 5-HT deficiency in certain limbic structures of the P rat may be a major neurobiological factor underlying their high alcohol drinking characteristics.

Original languageEnglish
Pages (from-to)170-177
Number of pages8
JournalDrug Development Research
Volume30
Issue number3
StatePublished - 1993

Fingerprint

Drinking Behavior
Alcohol Drinking
Serotonin
Alcohols
Rats
Dopamine
Serotonin 5-HT1 Receptors
Serotonin 5-HT3 Receptor Antagonists
Fenfluramine
5-Hydroxytryptophan
Ventral Tegmental Area
Fluoxetine
Nucleus Accumbens
Serotonin Uptake Inhibitors
Frontal Lobe
Hypothalamus
Neurons
Wistar Rats
Ethanol
Perfusion

Keywords

  • alcohol preference
  • dorsal raphe nucleus
  • nucleus accumbens
  • serotonin
  • ventral tegmental area

ASJC Scopus subject areas

  • Drug Discovery
  • Organic Chemistry
  • Pharmacology

Cite this

McBride, W. J., Murphy, J. M., Yoshimoto, K., Lumeng, L., & Li, T. K. (1993). Serotonin mechanisms in alcohol drinking behavior. Drug Development Research, 30(3), 170-177.

Serotonin mechanisms in alcohol drinking behavior. / McBride, W. J.; Murphy, J. M.; Yoshimoto, K.; Lumeng, L.; Li, T. K.

In: Drug Development Research, Vol. 30, No. 3, 1993, p. 170-177.

Research output: Contribution to journalArticle

McBride, WJ, Murphy, JM, Yoshimoto, K, Lumeng, L & Li, TK 1993, 'Serotonin mechanisms in alcohol drinking behavior', Drug Development Research, vol. 30, no. 3, pp. 170-177.
McBride WJ, Murphy JM, Yoshimoto K, Lumeng L, Li TK. Serotonin mechanisms in alcohol drinking behavior. Drug Development Research. 1993;30(3):170-177.
McBride, W. J. ; Murphy, J. M. ; Yoshimoto, K. ; Lumeng, L. ; Li, T. K. / Serotonin mechanisms in alcohol drinking behavior. In: Drug Development Research. 1993 ; Vol. 30, No. 3. pp. 170-177.
@article{6095af9bb76f4465a4d5b2cc70b479c3,
title = "Serotonin mechanisms in alcohol drinking behavior",
abstract = "Rat lines selectively bred for disparate alcohol-drinking behaviors exhibit innate differences in the contents of serotonin (5-HT) in several CNS limbic regions, e.g., nucleus accumbens (ACB), frontal cortex, hypothalamus, and olfactory tubercles. In these regions, the selectively bred alcohol-preferring (P) line has levels approximately 20{\%} (P < 0.05) lower than values obtained for the alcohol-nonpreferring (NP) line. In addition, in some limbic regions, the densities of (1) 5-HT1(A) receptors are higher by approximately 30{\%} and (2) 5-HT(1B) and 5-HT2 receptors are lower (by 25-40{\%}) in the P than in the NP line. Systemic administration of agents that increase synaptic levels of 5-HT, such as fluoxetine (a 5-HT uptake inhibitor), d-fenfluramine (a 5-HT releaser) and D, E-5-hydroxytryptophan (an immediate precursor of 5-HT), significantly decreased alcohol consumption of the P line of rats. Systemic (1.0 and 2.0 g/kg ip) administration or local perfusion (100 mM) of ethanol significantly increased the extracellular levels of 5-HT in the ACB of unselected Wistar rats. An interaction of the dorsal raphe nucleus (DRN) 5-HT system with the ventral tegmental area (VTA) dopamine (DA) pathway projecting to the ACB was indicated by the findings that DA release in the ACB increased and decreased following stimulation and inhibition, respectively, of DRN 5-HT neurons. Moreover, an involvement of 5-HT in mediating alcohol-stimulated DA release in the ACB is indicated by the observation that local application of a 5-HT3 antagonist can attenuate this stimulated release. Overall, the data suggest that an innate 5-HT deficiency in certain limbic structures of the P rat may be a major neurobiological factor underlying their high alcohol drinking characteristics.",
keywords = "alcohol preference, dorsal raphe nucleus, nucleus accumbens, serotonin, ventral tegmental area",
author = "McBride, {W. J.} and Murphy, {J. M.} and K. Yoshimoto and L. Lumeng and Li, {T. K.}",
year = "1993",
language = "English",
volume = "30",
pages = "170--177",
journal = "Drug Development Research",
issn = "0272-4391",
publisher = "John Wiley and Sons Inc.",
number = "3",

}

TY - JOUR

T1 - Serotonin mechanisms in alcohol drinking behavior

AU - McBride, W. J.

AU - Murphy, J. M.

AU - Yoshimoto, K.

AU - Lumeng, L.

AU - Li, T. K.

PY - 1993

Y1 - 1993

N2 - Rat lines selectively bred for disparate alcohol-drinking behaviors exhibit innate differences in the contents of serotonin (5-HT) in several CNS limbic regions, e.g., nucleus accumbens (ACB), frontal cortex, hypothalamus, and olfactory tubercles. In these regions, the selectively bred alcohol-preferring (P) line has levels approximately 20% (P < 0.05) lower than values obtained for the alcohol-nonpreferring (NP) line. In addition, in some limbic regions, the densities of (1) 5-HT1(A) receptors are higher by approximately 30% and (2) 5-HT(1B) and 5-HT2 receptors are lower (by 25-40%) in the P than in the NP line. Systemic administration of agents that increase synaptic levels of 5-HT, such as fluoxetine (a 5-HT uptake inhibitor), d-fenfluramine (a 5-HT releaser) and D, E-5-hydroxytryptophan (an immediate precursor of 5-HT), significantly decreased alcohol consumption of the P line of rats. Systemic (1.0 and 2.0 g/kg ip) administration or local perfusion (100 mM) of ethanol significantly increased the extracellular levels of 5-HT in the ACB of unselected Wistar rats. An interaction of the dorsal raphe nucleus (DRN) 5-HT system with the ventral tegmental area (VTA) dopamine (DA) pathway projecting to the ACB was indicated by the findings that DA release in the ACB increased and decreased following stimulation and inhibition, respectively, of DRN 5-HT neurons. Moreover, an involvement of 5-HT in mediating alcohol-stimulated DA release in the ACB is indicated by the observation that local application of a 5-HT3 antagonist can attenuate this stimulated release. Overall, the data suggest that an innate 5-HT deficiency in certain limbic structures of the P rat may be a major neurobiological factor underlying their high alcohol drinking characteristics.

AB - Rat lines selectively bred for disparate alcohol-drinking behaviors exhibit innate differences in the contents of serotonin (5-HT) in several CNS limbic regions, e.g., nucleus accumbens (ACB), frontal cortex, hypothalamus, and olfactory tubercles. In these regions, the selectively bred alcohol-preferring (P) line has levels approximately 20% (P < 0.05) lower than values obtained for the alcohol-nonpreferring (NP) line. In addition, in some limbic regions, the densities of (1) 5-HT1(A) receptors are higher by approximately 30% and (2) 5-HT(1B) and 5-HT2 receptors are lower (by 25-40%) in the P than in the NP line. Systemic administration of agents that increase synaptic levels of 5-HT, such as fluoxetine (a 5-HT uptake inhibitor), d-fenfluramine (a 5-HT releaser) and D, E-5-hydroxytryptophan (an immediate precursor of 5-HT), significantly decreased alcohol consumption of the P line of rats. Systemic (1.0 and 2.0 g/kg ip) administration or local perfusion (100 mM) of ethanol significantly increased the extracellular levels of 5-HT in the ACB of unselected Wistar rats. An interaction of the dorsal raphe nucleus (DRN) 5-HT system with the ventral tegmental area (VTA) dopamine (DA) pathway projecting to the ACB was indicated by the findings that DA release in the ACB increased and decreased following stimulation and inhibition, respectively, of DRN 5-HT neurons. Moreover, an involvement of 5-HT in mediating alcohol-stimulated DA release in the ACB is indicated by the observation that local application of a 5-HT3 antagonist can attenuate this stimulated release. Overall, the data suggest that an innate 5-HT deficiency in certain limbic structures of the P rat may be a major neurobiological factor underlying their high alcohol drinking characteristics.

KW - alcohol preference

KW - dorsal raphe nucleus

KW - nucleus accumbens

KW - serotonin

KW - ventral tegmental area

UR - http://www.scopus.com/inward/record.url?scp=0027717394&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0027717394&partnerID=8YFLogxK

M3 - Article

VL - 30

SP - 170

EP - 177

JO - Drug Development Research

JF - Drug Development Research

SN - 0272-4391

IS - 3

ER -