Cocaine Cues Drive Opposing Context-Dependent Shifts in Reward Processing and Emotional State

Department of Psychology, University of North Carolina, Chapel Hill, USA.
Biological psychiatry (Impact Factor: 10.26). 06/2011; 69(11):1067-74. DOI: 10.1016/j.biopsych.2011.02.014
Source: PubMed


Prominent neurobiological theories of addiction posit a central role for aberrant mesolimbic dopamine release but disagree as to whether repeated drug experience blunts or enhances this system. Although drug withdrawal diminishes dopamine release, drug sensitization augments mesolimbic function, and both processes have been linked to drug seeking. One possibility is that the dopamine system can rapidly switch from dampened to enhanced release depending on the specific drug-predictive environment. To test this, we examined dopamine release when cues signaled delayed cocaine delivery versus imminent cocaine self-administration.
Fast-scan cyclic voltammetry was used to examine real-time dopamine release while simultaneously monitoring behavioral indexes of aversion as rats experienced a sweet taste cue that predicted delayed cocaine availability and during self-administration. Furthermore, the impact of cues signaling delayed drug availability on intracranial self-stimulation, a broad measure of reward function, was assessed.
We observed decreased mesolimbic dopamine concentrations, decreased reward sensitivity, and negative affect in response to the cocaine-predictive taste cue that signaled delayed cocaine availability. Importantly, dopamine concentration rapidly switched to elevated levels to cues signaling imminent cocaine delivery in the subsequent self-administration session.
These findings show rapid, bivalent contextual control over brain reward processing, affect, and motivated behavior and have implications for mechanisms mediating substance abuse.

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Available from: Jeremy J Day, Oct 05, 2015
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    • "A key finding has been that different rewards such as cocaine, heroin, water, or sucrose induce phasic firing in largely different sets of neurons, which suggests that the stimulus properties of each reward are encoded in distinct ensembles (Cameron and Carelli, 2012; Carelli and Deadwyler, 1994; Carelli, 2002a; Carelli, 2002b; Carelli and Wondolowski, 2003; Chang et al., 1998; Deadwyler et al., 2004; Opris et al., 2009; Roop et al., 2002). Environmental cues associated with drug reward can also induce phasic firing either prior to drug reward presentation or during drug-free conditions (Carelli, 2002a; Chang et al., 1994; Chang et al., 1997b; Chang et al., 1998; Chang et al., 2000; Wheeler et al., 2011). Many of these neurons are activated only by cues that were previously associated with one reward (cocaine) but not by another reward (food) (Carelli and Ijames, 2001; Carelli, 2002b) which suggests that reward-associated cues or contexts are also encoded in distinct ensembles. "
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    ABSTRACT: Learned associations between drugs and environment play an important role in addiction and are thought to be encoded within specific patterns of sparsely distributed neurons called neuronal ensembles. This hypothesis is supported by correlational data from in vivo electrophysiology and cellular imaging studies in relapse models in rodents. In particular, cellular imaging with the immediate early gene c-fos and its protein product Fos has been used to identify sparsely distributed neurons that were strongly activated during conditioned drug behaviors such as drug self-administration and context- and cue-induced reinstatement of drug seeking. Here we review how Fos and the c-fos promoter have been employed to demonstrate causal roles for Fos-expressing neuronal ensembles in prefrontal cortex and nucleus accumbens in conditioned drug behaviors. This work has allowed identification of unique molecular and electrophysiological alterations within Fos-expressing neuronal ensembles that may contribute to the development and expression of learned associations in addiction.This article is part of a Special Issue entitled SI:Addiction circuits.
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    • "Thus, optogenetic disruption of dopamine cell activity during behavior results in robust behavioral outcomes, many of which resemble an aversive state (although see Chaudhury et al., 2013). That optical suppression of dopamine release induces indices of depression and aversion matches well with real-time recordings made of NAc dopamine concentration in response to aversive stimuli (Roitman et al., 2008; Wheeler et al., 2011; McCutcheon et al., 2012). "
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    Frontiers in Neural Circuits 09/2014; 8:114. DOI:10.3389/fncir.2014.00114 · 3.60 Impact Factor
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    • "Pharmacologic inhibition of the shell increases motivated behavior and hedonic responses to taste stimuli [93]. Consistent with these findings, Wheeler and colleagues, 2011 observed – through fast-scan cyclic voltammetry to examine real-time dopamine release in rats experiencing a sweet taste cue that predicted delayed cocaine availability and during self-administration- that dopamine release in this region, but not the core subregion, is rapidly elevated by palatable, and reduced by unpalatable, taste stimuli [94]. Furthermore, they showed that these rapid fluctuations in release can be altered by devaluation from learned associations, specifically the predictive and temporal relationship of the taste cue to cocaine availability. "
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    ABSTRACT: The ventral tegmental area is strongly associated with the reward system. Dopamine is released in areas such as the nucleus accumbens and prefrontal cortex as a result of rewarding experiences such as food, sex, and neutral stimuli that become associated with them. Electrical stimulation of the ventral tegmental area or its output pathways can itself serve as a potent reward. Different drugs that increase dopamine levels are intrinsically rewarding. Although the dopaminergic system represent the cornerstone of the reward system, other neurotransmitters such as endogenous opioids, glutamate, gamma-Aminobutyric acid, acetylcholine, serotonin, adenosine, endocannabinoids, orexins, galanin and histamine all affect this mesolimbic dopaminergic system. Consequently, genetic variations of neurotransmission are thought influence reward processing that in turn may affect distinctive social behavior and susceptibility to addiction. Here, we discuss current evidence on the orquestic regulation of different neurotranmitters on reward-seeking behavior and its potential effect on drug addiction.
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