Reverse microdialysis of a dopamine uptake inhibitor in the nucleus accumbens of alcohol-preferring rats

Effects on dialysate dopamine levels and ethanol intake

Eric Engleman, William J. McBride, Aaron A. Wilber, Saame R. Shaikh, Renee D. Eha, Lawrence Lumeng, Ting Kai Li, James M. Murphy

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Background: The mesolimbic dopamine (DA) system has been implicated in mediating the reinforcing actions of ethanol (EtOH). This study examines the effects of local perfusion of the DA uptake inhibitor GBR12909 (GBR) on (1) DA levels in the nucleus accumbens (NAc) and (2) EtOH drinking in alcohol- preferring rats. Methods: Stable drinking of a 15% (v/v) EtOH solution (minimum of 0.75 g/kg body weight) was established in daily 1 hr limited access sessions. Rats were then implanted with bilateral guide cannulae aimed 4 mm above the NAc. After recovery from surgery, concentric microdialysis probes (2 mm dialysis membrane surface) were inserted into the NAc. Most placements were in the shell or overlapping both shell and core. Two days later, the probes were perfused at 1.0μl/min with artificial cerebral spinal fluid (aCSF) for at least a 90 min washout period followed by collection of five basal samples over 150 min. Rats were then perfused with either aCSF alone or 10, 25, 100, or 200μM of GBR for 240 min on the first day of microdialysis. During the last 60 min of the drug treatment phase, rats were given their scheduled access to 15% EtOH. All rats were then perfused with aCSF for the last 90 min of the experiment. The following day, the procedure was repeated, but animals that received aCSF on the first day were given a dose of GBR and rats given GBR on the first day received only aCSF. Results: GBR perfusion increased extracellular NAc DA levels dose dependently to more than 800% of basal levels at 100 to 200μM but failed to alter EtOH intake (p > 0.05, paired t test) at any concentration tested. Moreover, after 100μM of GBR perfusion had terminated, the extracellular levels of DA in the NAc remained elevated for approximately 24 hr (790% of day 1 basal; p < 0.05). The increase in dialysate DA levels observed during GBR perfusion with 100μM was significantly greater for EtOH-experienced rats than for EtOH-naive rats [F(7,59) = 14.85, p < 0.0001, analysis of variance, Student-Newman-Keuls post hoc test]. Conclusions: The results suggest (1) that EtOH drinking experience induces neuroadaptations that increase DA release in the NAc, and (2) that additional elevation in synaptic levels of DA in the NAc does not influence the maintenance of ongoing alcohol drinking under scheduled access conditions in alcohol-preferring animals.

Original languageEnglish
Pages (from-to)795-801
Number of pages7
JournalAlcoholism: Clinical and Experimental Research
Volume24
Issue number6
StatePublished - Jun 2000

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Dopamine Uptake Inhibitors
Dialysis Solutions
Microdialysis
Nucleus Accumbens
Rats
Dopamine
Ethanol
Alcohols
Perfusion
Fluids
Alcohol Drinking
Drinking
Animals
Dialysis membranes
Drug therapy
Analysis of variance (ANOVA)
Surgery
Dialysis
Analysis of Variance
Body Weight

Keywords

  • Dopamine
  • Drinking
  • Ethanol
  • Microdialysis
  • Reinforcement

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Toxicology

Cite this

Reverse microdialysis of a dopamine uptake inhibitor in the nucleus accumbens of alcohol-preferring rats : Effects on dialysate dopamine levels and ethanol intake. / Engleman, Eric; McBride, William J.; Wilber, Aaron A.; Shaikh, Saame R.; Eha, Renee D.; Lumeng, Lawrence; Li, Ting Kai; Murphy, James M.

In: Alcoholism: Clinical and Experimental Research, Vol. 24, No. 6, 06.2000, p. 795-801.

Research output: Contribution to journalArticle

Engleman, Eric ; McBride, William J. ; Wilber, Aaron A. ; Shaikh, Saame R. ; Eha, Renee D. ; Lumeng, Lawrence ; Li, Ting Kai ; Murphy, James M. / Reverse microdialysis of a dopamine uptake inhibitor in the nucleus accumbens of alcohol-preferring rats : Effects on dialysate dopamine levels and ethanol intake. In: Alcoholism: Clinical and Experimental Research. 2000 ; Vol. 24, No. 6. pp. 795-801.
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abstract = "Background: The mesolimbic dopamine (DA) system has been implicated in mediating the reinforcing actions of ethanol (EtOH). This study examines the effects of local perfusion of the DA uptake inhibitor GBR12909 (GBR) on (1) DA levels in the nucleus accumbens (NAc) and (2) EtOH drinking in alcohol- preferring rats. Methods: Stable drinking of a 15{\%} (v/v) EtOH solution (minimum of 0.75 g/kg body weight) was established in daily 1 hr limited access sessions. Rats were then implanted with bilateral guide cannulae aimed 4 mm above the NAc. After recovery from surgery, concentric microdialysis probes (2 mm dialysis membrane surface) were inserted into the NAc. Most placements were in the shell or overlapping both shell and core. Two days later, the probes were perfused at 1.0μl/min with artificial cerebral spinal fluid (aCSF) for at least a 90 min washout period followed by collection of five basal samples over 150 min. Rats were then perfused with either aCSF alone or 10, 25, 100, or 200μM of GBR for 240 min on the first day of microdialysis. During the last 60 min of the drug treatment phase, rats were given their scheduled access to 15{\%} EtOH. All rats were then perfused with aCSF for the last 90 min of the experiment. The following day, the procedure was repeated, but animals that received aCSF on the first day were given a dose of GBR and rats given GBR on the first day received only aCSF. Results: GBR perfusion increased extracellular NAc DA levels dose dependently to more than 800{\%} of basal levels at 100 to 200μM but failed to alter EtOH intake (p > 0.05, paired t test) at any concentration tested. Moreover, after 100μM of GBR perfusion had terminated, the extracellular levels of DA in the NAc remained elevated for approximately 24 hr (790{\%} of day 1 basal; p < 0.05). The increase in dialysate DA levels observed during GBR perfusion with 100μM was significantly greater for EtOH-experienced rats than for EtOH-naive rats [F(7,59) = 14.85, p < 0.0001, analysis of variance, Student-Newman-Keuls post hoc test]. Conclusions: The results suggest (1) that EtOH drinking experience induces neuroadaptations that increase DA release in the NAc, and (2) that additional elevation in synaptic levels of DA in the NAc does not influence the maintenance of ongoing alcohol drinking under scheduled access conditions in alcohol-preferring animals.",
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T2 - Effects on dialysate dopamine levels and ethanol intake

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AU - McBride, William J.

AU - Wilber, Aaron A.

AU - Shaikh, Saame R.

AU - Eha, Renee D.

AU - Lumeng, Lawrence

AU - Li, Ting Kai

AU - Murphy, James M.

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N2 - Background: The mesolimbic dopamine (DA) system has been implicated in mediating the reinforcing actions of ethanol (EtOH). This study examines the effects of local perfusion of the DA uptake inhibitor GBR12909 (GBR) on (1) DA levels in the nucleus accumbens (NAc) and (2) EtOH drinking in alcohol- preferring rats. Methods: Stable drinking of a 15% (v/v) EtOH solution (minimum of 0.75 g/kg body weight) was established in daily 1 hr limited access sessions. Rats were then implanted with bilateral guide cannulae aimed 4 mm above the NAc. After recovery from surgery, concentric microdialysis probes (2 mm dialysis membrane surface) were inserted into the NAc. Most placements were in the shell or overlapping both shell and core. Two days later, the probes were perfused at 1.0μl/min with artificial cerebral spinal fluid (aCSF) for at least a 90 min washout period followed by collection of five basal samples over 150 min. Rats were then perfused with either aCSF alone or 10, 25, 100, or 200μM of GBR for 240 min on the first day of microdialysis. During the last 60 min of the drug treatment phase, rats were given their scheduled access to 15% EtOH. All rats were then perfused with aCSF for the last 90 min of the experiment. The following day, the procedure was repeated, but animals that received aCSF on the first day were given a dose of GBR and rats given GBR on the first day received only aCSF. Results: GBR perfusion increased extracellular NAc DA levels dose dependently to more than 800% of basal levels at 100 to 200μM but failed to alter EtOH intake (p > 0.05, paired t test) at any concentration tested. Moreover, after 100μM of GBR perfusion had terminated, the extracellular levels of DA in the NAc remained elevated for approximately 24 hr (790% of day 1 basal; p < 0.05). The increase in dialysate DA levels observed during GBR perfusion with 100μM was significantly greater for EtOH-experienced rats than for EtOH-naive rats [F(7,59) = 14.85, p < 0.0001, analysis of variance, Student-Newman-Keuls post hoc test]. Conclusions: The results suggest (1) that EtOH drinking experience induces neuroadaptations that increase DA release in the NAc, and (2) that additional elevation in synaptic levels of DA in the NAc does not influence the maintenance of ongoing alcohol drinking under scheduled access conditions in alcohol-preferring animals.

AB - Background: The mesolimbic dopamine (DA) system has been implicated in mediating the reinforcing actions of ethanol (EtOH). This study examines the effects of local perfusion of the DA uptake inhibitor GBR12909 (GBR) on (1) DA levels in the nucleus accumbens (NAc) and (2) EtOH drinking in alcohol- preferring rats. Methods: Stable drinking of a 15% (v/v) EtOH solution (minimum of 0.75 g/kg body weight) was established in daily 1 hr limited access sessions. Rats were then implanted with bilateral guide cannulae aimed 4 mm above the NAc. After recovery from surgery, concentric microdialysis probes (2 mm dialysis membrane surface) were inserted into the NAc. Most placements were in the shell or overlapping both shell and core. Two days later, the probes were perfused at 1.0μl/min with artificial cerebral spinal fluid (aCSF) for at least a 90 min washout period followed by collection of five basal samples over 150 min. Rats were then perfused with either aCSF alone or 10, 25, 100, or 200μM of GBR for 240 min on the first day of microdialysis. During the last 60 min of the drug treatment phase, rats were given their scheduled access to 15% EtOH. All rats were then perfused with aCSF for the last 90 min of the experiment. The following day, the procedure was repeated, but animals that received aCSF on the first day were given a dose of GBR and rats given GBR on the first day received only aCSF. Results: GBR perfusion increased extracellular NAc DA levels dose dependently to more than 800% of basal levels at 100 to 200μM but failed to alter EtOH intake (p > 0.05, paired t test) at any concentration tested. Moreover, after 100μM of GBR perfusion had terminated, the extracellular levels of DA in the NAc remained elevated for approximately 24 hr (790% of day 1 basal; p < 0.05). The increase in dialysate DA levels observed during GBR perfusion with 100μM was significantly greater for EtOH-experienced rats than for EtOH-naive rats [F(7,59) = 14.85, p < 0.0001, analysis of variance, Student-Newman-Keuls post hoc test]. Conclusions: The results suggest (1) that EtOH drinking experience induces neuroadaptations that increase DA release in the NAc, and (2) that additional elevation in synaptic levels of DA in the NAc does not influence the maintenance of ongoing alcohol drinking under scheduled access conditions in alcohol-preferring animals.

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KW - Drinking

KW - Ethanol

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KW - Reinforcement

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