Sensitization of ventral tegmental area dopamine neurons to the stimulating effects of ethanol

Zheng Ming Ding, Zachary Rodd, Eric Engleman, William J. McBride

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

Background: Previous studies indicated that chronic alcohol drinking increased the sensitivity of the posterior ventral tegmental area (p-VTA) to the reinforcing effects of ethanol. The current study tested the hypothesis that local exposure of the p-VTA to ethanol would increase the sensitivity of dopamine (DA) neurons to the stimulating effects of ethanol. Methods: Experiment 1 examined the stimulating effects of ethanol in the p-VTA after a 7-day ethanol pretreatment in the p-VTA. Adult female Wistar rats were pretreated with microinjections of 200 mg% ethanol or artificial cerebrospinal fluid (aCSF) into the p-VTA once a day for 7 days. On the eighth day, rats received a challenge injection of ethanol (100, 200, or 300 mg%) or aCSF into the p-VTA, and extracellular DA levels were measured in the nucleus accumbens (NAc) shell with microdialysis. Experiment 2 examined the stimulating effects of ethanol (200 mg%) after a 3- or 5-day ethanol (200 mg%) pretreatment in the p-VTA. Experiment 3 examined the stimulating effects of ethanol (200 mg%) 7 days after the last of the 7-day ethanol (200 mg%) pretreatments in the p-VTA. Results: Experiment 1: in both aCSF- and ethanol-pretreated rats, the challenge microinjection of ethanol dose-dependently increased DA release in the NAc shell, with significantly greater increases in ethanol-pretreated groups. Experiment 2: the 5-day, but not 3-day, ethanol pretreatment protocol increased the response of p-VTA dopamine neurons to the ethanol challenge. Experiment 3: the increased stimulating effects of ethanol were still evident after 7 days. Conclusions: The results indicate that repeated local ethanol exposure of the p-VTA produced neuroadaptations in DA neurons projecting to the NAc shell, resulting in a persistent increase in the sensitivity of these neurons to the stimulating effects of ethanol.

Original languageEnglish
Pages (from-to)1571-1581
Number of pages11
JournalAlcoholism: Clinical and Experimental Research
Volume33
Issue number9
DOIs
StatePublished - Sep 2009

Fingerprint

Ventral Tegmental Area
Dopaminergic Neurons
Neurons
Dopamine
Ethanol
Cerebrospinal fluid
Nucleus Accumbens
Cerebrospinal Fluid
Rats
Experiments
Microinjections

Keywords

  • Dopamine
  • Ethanol
  • Microdialysis
  • Nucleus accumbens
  • Sensitization
  • Ventral tegmental area

ASJC Scopus subject areas

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

Cite this

Sensitization of ventral tegmental area dopamine neurons to the stimulating effects of ethanol. / Ding, Zheng Ming; Rodd, Zachary; Engleman, Eric; McBride, William J.

In: Alcoholism: Clinical and Experimental Research, Vol. 33, No. 9, 09.2009, p. 1571-1581.

Research output: Contribution to journalArticle

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abstract = "Background: Previous studies indicated that chronic alcohol drinking increased the sensitivity of the posterior ventral tegmental area (p-VTA) to the reinforcing effects of ethanol. The current study tested the hypothesis that local exposure of the p-VTA to ethanol would increase the sensitivity of dopamine (DA) neurons to the stimulating effects of ethanol. Methods: Experiment 1 examined the stimulating effects of ethanol in the p-VTA after a 7-day ethanol pretreatment in the p-VTA. Adult female Wistar rats were pretreated with microinjections of 200 mg{\%} ethanol or artificial cerebrospinal fluid (aCSF) into the p-VTA once a day for 7 days. On the eighth day, rats received a challenge injection of ethanol (100, 200, or 300 mg{\%}) or aCSF into the p-VTA, and extracellular DA levels were measured in the nucleus accumbens (NAc) shell with microdialysis. Experiment 2 examined the stimulating effects of ethanol (200 mg{\%}) after a 3- or 5-day ethanol (200 mg{\%}) pretreatment in the p-VTA. Experiment 3 examined the stimulating effects of ethanol (200 mg{\%}) 7 days after the last of the 7-day ethanol (200 mg{\%}) pretreatments in the p-VTA. Results: Experiment 1: in both aCSF- and ethanol-pretreated rats, the challenge microinjection of ethanol dose-dependently increased DA release in the NAc shell, with significantly greater increases in ethanol-pretreated groups. Experiment 2: the 5-day, but not 3-day, ethanol pretreatment protocol increased the response of p-VTA dopamine neurons to the ethanol challenge. Experiment 3: the increased stimulating effects of ethanol were still evident after 7 days. Conclusions: The results indicate that repeated local ethanol exposure of the p-VTA produced neuroadaptations in DA neurons projecting to the NAc shell, resulting in a persistent increase in the sensitivity of these neurons to the stimulating effects of ethanol.",
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