Regional Effects of Cocaine on Phasic Dopamine Release in the Nucleus Accumbens: A Role for the Hindbrain

Cocaine increases dopamine concentration in the nucleus accumbens through competitive inhibition of the dopamine transporter (DAT) in this terminal region. However, it also increases the frequency of dopamine release events, a finding that cannot be explained by action at the DAT alone. Rather, this effect may be mediated by cocaine-induced modulation of brain regions that project to dopamine neurons. To explore regional contributions of cocaine to phasic dopamine signaling, cocaine was administered into the lateral or fourth ventricles and compared the effects on electrically-evoked dopamine in the nucleus accumbens to that of systemically delivered cocaine. Each stimulation train resulted in a rapid and pronounced rise in dopamine followed by a rapid return to baseline as measured by fast-scan cyclic voltammetry. The magnitude of dopamine release ([DA]max) as well as the latency to decay to fifty percent of the maximum (t(1/2); index of DAT activity) by each stimulation train were recorded. Rats received an injection of cocaine [systemic: 2.5mg/kg; lateral and fourth ventricle: 50ug in 1ul) or an equal volume of vehicle. All routes of cocaine delivery caused an increase in [DA]max. However, only systemic cocaine caused an increase in t(1/2). That hindbrain-delivered (fourth ventricle) cocaine caused an increase in [DA]max is novel. Together, the data demonstrate that cocaine-induced effects on phasic dopamine signaling are mediated via actions throughout the brain including the hindbrain.