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

Abstract

Mesolimbic dopamine neurons projecting from the ventral tegmental area (VTA) to the nucleus accumbens (NAc) are part of a complex circuit mediating cocaine-directed behaviors. However, the precise role of rapid (subsecond) dopamine release within the primary sub-regions of the NAc, the core and shell, and its relationship to NAc cell firing during this behavior remain unknown. Here, using fast-scan cyclic voltammetry (FSCV) we report rapid dopamine signaling in both the core and shell, however, significant differences were observed in the timing of dopamine release events within seconds of the cocaine reinforced response during self-administration sessions. Importantly, simultaneous voltammetric and electrophysiological recordings from the same electrode reveal that, at certain sites within both sub-regions, neurons exhibiting patterned activation were observed at locations where rapid dopamine release was present; the greater the strength of the neural signal the larger the dopamine release event. In addition, it was at those locations that electrically-evoked stimulated release was greatest. No changes in dopamine were observed where nonphasic neurons were recorded. Thus, although differences are evident in dopamine release dynamics relative to cocaine-reinforced responding within the core and shell, dopamine release is heterogeneous within each structure and varies as a function of precise neuronal targets during cocaine-seeking behavior.

Hierarchical recruitment of phasic dopamine signaling in the striatum during the progression of cocaine use

“…S2). This increase produced an average change in dopamine concentration over the 7 s following the response of 7.77 ± 1.69 nM, with a mean peak of 13.47 ± 2.16 nM occurring 2.45 ± 0.26 s after the response and returning to baseline at 7.41 ± 0.28 s. These kinetics are similar to those reported in previous studies following a comparable amount of training (5)(6)(7)(8), and the concentration matches those from recordings in the VMS with unbiased recording site selection (8), as in the current study (SI Discussion and Fig. S3).…”

“…The ambient concentration of dopamine in the VMS is increased when animals self-administer drugs of abuse, including cocaine (3), and animals maintain this elevated dopamine level by regulating their rate of responding for drug (4). In addition, with repeated pairing of environmental stimuli with the drug, these CS also gain the propensity to elicit changes in dopamine concentration in the VMS (5)(6)(7)(8); and even though these phasic neurochemical responses last only a few seconds, they are capable of controlling drug-seeking and -taking behavior (5). Together, these results implicate dopamine release in the VMS as a critical substrate in the control of drug use (2,3,9).…”

Genetic background and epigenetic modifications in the core of the nucleus accumbens predict addiction-like behavior in a rat model

“…During the cue-induced reinstatement test, responses in the active nose-port resulted in the presentation of the discrete cue light previously associated with cocaine delivery (45). Under these conditions, bHRs respond much more vigorously for presentation of the cue light relative to bLRs: Effect of Phenotype [F (1,28) = 9.4, P = 0.005]; Effect of Port [F (1,28) = 18.3, P = 0.0002]; Phenotype × Port interaction, F (1, 28) = 6.4, P = 0.017] (Fig. 5D).…”

Food and Drug Reward: Overlapping Circuits in Human Obesity and Addiction

“…Imaging DA in response to drugs and to conditioned cues in addiction DA's role in reinforcement is more complex than just coding for reward per se (hedonic pleasure) and stimuli that induce fast and large DA increases also trigger conditioned responses and elicit incentive motivation to procure them (Owesson-White et al 2009). This is important because, through the process of conditioning, neutral stimuli that are linked to the reinforcer (whether a natural reinforcer or a drug) acquire the ability by themselves to increase DA in striatum (including NAc) in anticipation of the reward, thus engendering a strong motivation to seek the drug (Owesson-White et al 2009).…”