Neural encoding of cocaine-seeking behavior is coincident with phasic dopamine release in the accumbens core and shell.

Representative dopamine release dynamics in the core and shell relative to a lever press response for intravenous cocaineTwo-dimensional color representation of cyclic voltammetric data collected for 20 s around single self-administration trials in the core (A) and shell (B). The applied voltage (Eapp) is the ordinate and the abscissa is time (t(s) = time in seconds here and in subsequent figures). Changes in current at the carbon-fiber electrode are indicated in color; dopamine has features at 0.6 V on the positive-going scan and −0.2 V on the negative going scan. Differential [DA] concentrations determined via principal component analysis are plotted above color plots.

Average voltammetric data measured in the core and shell relative to cocaine-reinforced responding across all animalsMean (solid line) ± SEM (dashed line) changes in dopamine relative to the reinforced response (R) across all animals in the core (A, n = 4) and shell (B, n = 4). Averages were determined for each animal, then averaged together; only full sessions were included. The dashed bar shows the time of R and the horizontal line indicates the drug-infusion period. Asterisks indicate significant increases in dopamine relative to baseline concentrations (p ≤ 0.05).

A representative example of combined electrochemical and electrophysiological recordings in the NAc shell during a cocaine self-administration sessionUpper panel: average of voltammetric data recorded during nine lever-press responses shown as a color representation of the data as in Figure 1. The dopamine signal rises before the lever press, declines slightly after the response, and then rises again. Middle: raster display of single-unit activity on the same trials. Bottom: PEH of the data in the middle panel; the cell was classified as type RFe. The dopamine concentration determined from the color plot by principal component analysis is shown as a blue trace superimposed on the PEH.

Dopamine changes around the lever press for cocaine sorted by type of neural activity of adjacent neuronsPEHs show population firing of neurons relative to lever press responding for intravenous cocaine (indicated by dashed lines at R). Increases in mean [DA] (solid blue lines) ± SEM (dashed blue lines) are superimposed above each PEH; averages were determined for each session, then averaged together here and in Figure 6. They were recorded at the same locations as the unit activity. A. Type PR (n = 14 cells), B. Type RFe (n = 6 cells), C. Type RFi (n = 5 of 9 cells), D. Type NP (n=46 cells). ANOVAs revealed significant overall increases in dopamine concentration at locations at which types PR, RFe and RFi cells were recorded; asterisks indicate significant increases relative to baseline (p ≤ 0.05). No significant changes in [DA] were measured at locations where type NP cells were recorded. ns = non significant.

Linear regression analyses correlating signal-to-baseline (S:B) ratios for peak [DA]s versus S:B ratios for peak changes in NAc cell firing across cell types. A. For excitatory neurons (types PR and RFe) a significant positive linear regression was observed. B. For inhibitory neurons (type RFi) a significant negative linear regression was evident.

Dopamine changes around the lever press for cocaine sorted by NAc subregion and degree of phasic activityDopamine concentrations at locations where NP neurons were recorded in the core (A) or shell (B) reveal no significant increases in dopamine release events. In contrast, when dopamine concentration changes were plotted at sites in which only phasic (type PR, RFe and RFi) cells were recorded, significant increases in dopamine was observed in both the core (C) and shell (D). Mean [DA] indicated by solid lines; SEM indicated by dashed lines. Asterisks indicate significant increases in dopamine * p ≤ 0.05, ** p ≤ 0.01. R is reinforced response.

Histological reconstruction of electrode tip locationsCoronal sections of the rat brain depicting electrode tip placements (stars) in the core and shell of the NAc. Sections are from the stereotaxic atlas of (Paxinos & Watson, 1986).