Long-term reduction in ventral tegmental area dopamine neuron population activity following repeated stimulant or ethanol treatment

Background: Drugs of abuse exert profound effects on the mesolimbic/mesocortical dopaminergic (DA) systems. Few studies have investigated the long-term adaptations in ventral tegmental area (VTA) DA neuron activity after repeated exposure to drugs of abuse. We investigated changes in the electrical activity of VTA DA neurons after cessation from treatment with several stimulants and ethanol. Methods. Adult rats were treated with stimulants (amphetamine: 2 mg/kg per day, 5 days/week, 2 weeks, cocaine: 15 mg/kg per day, 5 days/week, 2 weeks; nicotine: .5 mg/kg per day, 5 days; ethanol: 10 g/kg per day, 3 weeks) and the single-unit activity of VTA DA neurons was studied in vivo 3 to 6 weeks later. Results. Stimulant and ethanol treatment decreased basal VTA DA neuron population activity but not firing rate or firing pattern. This effect was reversed by acute apomorphine, suggesting that the underlying mechanism for reduced population activity was depolarization inactivation. Anesthesia did not confound this result, as similar effects were observed in amphetamine-treated rats recorded in a conscious preparation. Conclusions: Reduced basal VTA DA neuron population activity presumably due to depolarization inactivation is a common and long-term neuroadaptation to repeated treatment with stimulants and ethanol. This change in VTA DA neuron activity could underlie the persistent nature of addiction-associated behaviors.