A single, moderate ethanol exposure alters extracellular dopamine levels and dopamine D2 receptor function in the nucleus accumbens of wistar rats

James M. Murphy, Kelle M. Franklin, Eric Engleman, Cynthia M. Ingraham, Joseph A. McClaren, Carrie M. Keith, William J. McBride

Research output: Contribution to journalArticle

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Abstract

Background: The nucleus accumbens (NAc) has been implicated in the neurochemical effects of ethanol (EtOH). Evidence suggests that repeated EtOH exposures and chronic EtOH drinking increase dopamine (DA) neurotransmission in the NAc due, in part, to a reduction in D2 autoreceptor function. The objectives of the current study were to evaluate the effects of a single EtOH pretreatment and repeated EtOH pretreatments on DA neurotransmission and D 2 autoreceptor function in the NAc of Wistar rats. Methods: Experiment 1 examined D2 receptor function after a single intraperitoneal (i.p.) injection or repeated i.p. injections of 0.0, 0.5, 1.0, or 2.0 g/kg EtOH to female Wistar rats. Single EtOH pretreatment groups received 1 daily i.p. injection of 0.9% NaCl (saline) for 4 days, followed by 1 day of saline or EtOH administration; repeated EtOH pretreatment groups received 5 days of saline or EtOH injections. Reverse microdialysis experiments were conducted to determine the effects of local perfusion with the D2-like receptor antagonist (-)sulpiride (SUL; 100 uM), on extracellular DA levels in the NAc. Experiment 2 evaluated if pretreatment with a single, moderate (1.0 g/kg) dose of EtOH would alter levels and clearance of extracellular DA in the NAc, as measured by no-net-flux (NNF) microdialysis. Subjects were divided into the EtOH-naïve and the single EtOH pretreated groups from Experiment 1. Results: Experiment 1: Changes in extracellular DA levels induced with SUL perfusion were altered by the EtOH dose (p <0.001), but not the number of EtOH pretreatments (p > 0.05). Post-hoc analyses indicated that groups pretreated with single or repeated 1.0 g/kg EtOH showed significantly attenuated DA response to SUL, compared with all other groups (p <0.001). Experiment 2: Multiple linear regression analyses yielded significantly (p <0.05) higher extracellular DA concentrations in the NAc of rats receiving EtOH pretreatment, compared with their EtOH-naïve counterparts (3.96 ± 0.42 nM and 3.25 ± 0.23 nM, respectively). Extraction fractions were not significantly different between the 2 groups. Conclusions: The present results indicate that a single EtOH pretreatment at a moderate dose can increase DA neurotransmission in the NAc due, in part, to reduced D2 autoreceptor function.

Original languageEnglish (US)
Pages (from-to)1721-1730
Number of pages10
JournalAlcoholism: Clinical and Experimental Research
Volume33
Issue number10
DOIs
StatePublished - Oct 2009
Externally publishedYes

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Dopamine D2 Receptors
Nucleus Accumbens
Wistar Rats
Rats
Dopamine
Ethanol
Autoreceptors
Intraperitoneal Injections
Synaptic Transmission
Experiments
Microdialysis
Perfusion
Sulpiride
Linear regression
Drinking
Linear Models
Regression Analysis
Fluxes
Injections

Keywords

  • D2 autoreceptor
  • Dopamine
  • Ethanol
  • Microdialysis
  • Nucleus accumbens

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Psychiatry and Mental health
  • Toxicology

Cite this

A single, moderate ethanol exposure alters extracellular dopamine levels and dopamine D2 receptor function in the nucleus accumbens of wistar rats. / Murphy, James M.; Franklin, Kelle M.; Engleman, Eric; Ingraham, Cynthia M.; McClaren, Joseph A.; Keith, Carrie M.; McBride, William J.

In: Alcoholism: Clinical and Experimental Research, Vol. 33, No. 10, 10.2009, p. 1721-1730.

Research output: Contribution to journalArticle

Murphy, James M. ; Franklin, Kelle M. ; Engleman, Eric ; Ingraham, Cynthia M. ; McClaren, Joseph A. ; Keith, Carrie M. ; McBride, William J. / A single, moderate ethanol exposure alters extracellular dopamine levels and dopamine D2 receptor function in the nucleus accumbens of wistar rats. In: Alcoholism: Clinical and Experimental Research. 2009 ; Vol. 33, No. 10. pp. 1721-1730.
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T1 - A single, moderate ethanol exposure alters extracellular dopamine levels and dopamine D2 receptor function in the nucleus accumbens of wistar rats

AU - Murphy, James M.

AU - Franklin, Kelle M.

AU - Engleman, Eric

AU - Ingraham, Cynthia M.

AU - McClaren, Joseph A.

AU - Keith, Carrie M.

AU - McBride, William J.

PY - 2009/10

Y1 - 2009/10

N2 - Background: The nucleus accumbens (NAc) has been implicated in the neurochemical effects of ethanol (EtOH). Evidence suggests that repeated EtOH exposures and chronic EtOH drinking increase dopamine (DA) neurotransmission in the NAc due, in part, to a reduction in D2 autoreceptor function. The objectives of the current study were to evaluate the effects of a single EtOH pretreatment and repeated EtOH pretreatments on DA neurotransmission and D 2 autoreceptor function in the NAc of Wistar rats. Methods: Experiment 1 examined D2 receptor function after a single intraperitoneal (i.p.) injection or repeated i.p. injections of 0.0, 0.5, 1.0, or 2.0 g/kg EtOH to female Wistar rats. Single EtOH pretreatment groups received 1 daily i.p. injection of 0.9% NaCl (saline) for 4 days, followed by 1 day of saline or EtOH administration; repeated EtOH pretreatment groups received 5 days of saline or EtOH injections. Reverse microdialysis experiments were conducted to determine the effects of local perfusion with the D2-like receptor antagonist (-)sulpiride (SUL; 100 uM), on extracellular DA levels in the NAc. Experiment 2 evaluated if pretreatment with a single, moderate (1.0 g/kg) dose of EtOH would alter levels and clearance of extracellular DA in the NAc, as measured by no-net-flux (NNF) microdialysis. Subjects were divided into the EtOH-naïve and the single EtOH pretreated groups from Experiment 1. Results: Experiment 1: Changes in extracellular DA levels induced with SUL perfusion were altered by the EtOH dose (p <0.001), but not the number of EtOH pretreatments (p > 0.05). Post-hoc analyses indicated that groups pretreated with single or repeated 1.0 g/kg EtOH showed significantly attenuated DA response to SUL, compared with all other groups (p <0.001). Experiment 2: Multiple linear regression analyses yielded significantly (p <0.05) higher extracellular DA concentrations in the NAc of rats receiving EtOH pretreatment, compared with their EtOH-naïve counterparts (3.96 ± 0.42 nM and 3.25 ± 0.23 nM, respectively). Extraction fractions were not significantly different between the 2 groups. Conclusions: The present results indicate that a single EtOH pretreatment at a moderate dose can increase DA neurotransmission in the NAc due, in part, to reduced D2 autoreceptor function.

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KW - D2 autoreceptor

KW - Dopamine

KW - Ethanol

KW - Microdialysis

KW - Nucleus accumbens

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