Exciting inhibition in psychostimulant addiction

Neuroplasticity induced in the nucleus accumbens by repeated psychostimulant administration is thought to underlie the vulnerability to relapse in addicts. Electrophysiological research presents a contradictory portrait of psychostimulant-induced neuroplasticity, reflecting both increases and decreases in excitatory transmission. Drug-induced adaptations of ionic conductances decrease the intrinsic excitability of individual nucleus accumbens spiny neurons but, in the context of the circuitry in which these neurons are embedded, such reduced intrinsic excitability increases the salience of excitatory drive that is elicited by drug-associated stimuli. Thus, we propose that reduced basal excitability, combined with enhanced excitatory drive by drug-associated stimuli, contributes to the two cardinal features of addiction: reduced responding to natural reward and enduring vulnerability to relapse.