Reverse microdialysis of a dopamine uptake inhibitor in the nucleus accumbens of alcohol-preferring rats: Effects on dialysate dopamine levels and ethanol intake

Background: The mesolimbic dopamine (DA) system has been implicated in medi ating the reinforcing actions of ethanol (EtOH). This study examines the ef fects of local perfusion of the DA uptake inhibitor GBR12909 (GBR) on (1) D A levels in the nucleus accumbens (NAc) and (2) EtOH drinking in alcohol-pr eferring 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 w ere 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 p erfused at 1.0 mu l/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, 10 0, or 200 mu M 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 schedul ed access to 15% EtOH. All rats were then perfused with aCSF for the last 9 0 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 r ats given GBR on the first day received only aCSF. Results: GBR perfusion increased extracellular NAc DA levels dose dependent ly to more than 800% of basal levels at 100 to 200 mu M but failed to alter EtOH intake (p > 0.05, paired t test) at any concentration tested. Moreove r, after 100 mu M of GBR perfusion had terminated, the extracellular levels of DA in the NAc remained elevated for approximately 24 hr (790% of day I basal; p < 0.05). The increase in dialysate DA levels observed during GBR p erfusion with 100 mu M 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 addition al elevation in synaptic levels of DA in the NAc does not influence the mai ntenance of ongoing alcohol drinking under scheduled access conditions in a lcohol-preferring animals.