Adolescent social isolation associated changes in ethanol-induced dopamine regulation in the ventral pallidum

Abstract

Adolescent social isolation (aSI) has been demonstrated to increase anxiety-like behavior and ethanol consumption. The ventral pallidum (VP), a basal ganglia structure that receives dopaminergic projections from the VTA, contributes to reward and aversion processing, and is highly responsive to psychosocial stressors. In our study, we sought to characterize the effects of aSI on maladaptive behavioral phenotypes such as anxiety-like behavior, ethanol consumption, and aversion-resistant ethanol-intake as measured by the consumption of ethanol (20 %, v/v) adulterated with the bitterant quinine (0, 3, 10, 30, 100 mg/l). We further used ex vivo fast scan cyclic voltammetry (FSCV) to probe dopamine release kinetics in the VP in response to aSI following both tonic and phasic stimulation. Finally, we measured the impact of an acute application of ethanol (80 mM, 150 mM) on dopamine release kinetics in the VP following both tonic and phasic stimulation. Our results indicated that aSI potentiates anxiety-like behavior and ethanol preference, but does not promote aversion-resistant ethanol drinking. While pallidal dopamine release kinetics were insensitive to aSI at baseline, ethanol perfused over slices containing the VP modulated tonic dopamine release in all rats, albeit at a lower magnitude in aSI rats. Furthermore, ethanol modulated phasic dopamine release in a stress-dependent and sex-specific manner. Thus, dopamine in the VP may contribute to the maladaptive consumption of ethanol following aSI, though the exact mechanism may be different between male and female rats.