Psychostimulant effects on dopamine uptake.

<p>Data are the mean ± SEM.</p>**<p>, significantly different from saline (<i>p</i><0.01).</p

Averaged psychostimulant- and stimulation-dependent effects.

<p><b>A.</b> The maximal concentration of electrically evoked dopamine ([DA]_max). <b>B.</b> Vesicular release ([DA]_p). Stimulus duration is shown along the x axis. Psychostimulants differentially elicited stimulus-dependent effects on [DA]_max and [DA]_p. Data are the ratio of post-drug over pre-drug response (Post/Pre) for the dorsal (left) and ventral (right) striatum and are expressed as mean ± SEM. *, significantly different from saline (<i>p</i><0.05).</p

Representative effects of AMPH on phasic dopamine signaling in the ventral striatum.

<p><b>A.</b> Pre-drug. <b>B.</b> Post-AMPH. Traces show 90 s of a recording with a short-duration (0.4 s) stimulation applied at 5 s (see line underneath). The color plot serially displaying all background-subtracted cyclic voltammograms is shown underneath. <b>INSET.</b> Time-expanded view. Individual background-subtracted voltammograms are shown at the top left and compare dopamine collected during the evoked phasic-like response (black line) to pre-drug baseline (<b>A.</b>) or a dopamine transient collected post-drug (<b>B.</b>) as indicated by vertical white line in the pseudocolot plot (red line).</p

Sensitization of Rapid Dopamine Signaling in the Nucleus Accumbens Core and Shell After Repeated Cocaine in Rats

Repeated cocaine exposure and withdrawal leads to long-term changes, including behavioral and dopamine sensitization to an acute cocaine challenge, that are most pronounced after long withdrawal periods. However, the changes in dopamine neurotransmission after short withdrawal periods are less well defined. To study dopamine neurotransmission after 1-day withdrawal, we used fast-scan cyclic voltammetry (FSCV) to determine whether repeated cocaine alters rapid dopamine release and uptake in the nucleus accumbens (NAc) core and shell. FSCV was performed in urethane anesthetized male Sprague-Dawley rats that had previously received one or seven daily injections of saline or cocaine (15 mg/kg, ip). In response to acute cocaine, subjects showed increased dopamine overflow that resulted from both increased dopamine release and slowed dopamine uptake. One-day cocaine pre-exposure, however, did not alter dopaminergic responses to a subsequent cocaine challenge. In contrast, 7-day cocaine-treated subjects showed a potentiated rapid dopamine response in both the core and shell after an acute cocaine challenge. In addition, kinetic analysis during the cocaine challenge showed a greater increase in apparent Km of 7-day cocaine exposed subjects. Together, the data provide the first in vivo demonstration of rapid dopamine sensitization in the NAc core and shell after a short withdrawal period. In addition, the data clearly delineate cocaine's release and uptake effects and suggest that the observed sensitization results from greater uptake inhibition in cocaine pre-exposed subjects