Elsevier

Biological Psychiatry

Volume 69, Issue 11, 1 June 2011, Pages 1067-1074
Biological Psychiatry

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

https://doi.org/10.1016/j.biopsych.2011.02.014Get rights and content

Background

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.

Methods

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.

Results

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.

Conclusions

These findings show rapid, bivalent contextual control over brain reward processing, affect, and motivated behavior and have implications for mechanisms mediating substance abuse.

Section snippets

Subjects

Twenty-four male Sprague–Dawley rats (300–350 g) were individually housed with ad libitum food and water with a 12/12 hour light/dark cycle. All experiments were conducted in the light phase and approved by the Institutional Animal Care and Use Committee at the University of North Carolina, Chapel Hill.

Experimenter-Delivered Cocaine

Naive rats were implanted with intraoral catheters as described previously (13). After recovery, rats were given daily drug conditioning sessions (Figure 1A). In each session, mildly

Results

Before investigating cocaine-conditioned effects on dopamine release, we examined the effect of intraoral infusions of palatable and unpalatable taste stimuli on dopamine release in the shell and core subregions of the NAc, because these regions have different roles in the regulation of reward-related behavior (30, 31, 32). Measurements were made using fast-scan cyclic voltammetry, an electrochemical technique with the temporal resolution necessary for distinguishing rapid changes in dopamine

Discussion

Here, we demonstrate that taste stimuli signaling delayed cocaine availability can induce a negative affective state that alters hedonic sensitivity, brain reward processing, and motivated behavior. We observed the emergence of negative affect and reduced dopamine release using taste cues that signaled delayed cocaine availability when presented before cocaine self-administration. Later, in the same session, dopamine release was enhanced to cues that signaled imminent cocaine delivery during

References (50)

  • S.J. Robbins et al.

    Mood state and recent cocaine use are not associated with levels of cocaine cue reactivity

    Drug Alcohol Depend

    (2000)
  • S.E. Hyman et al.

    Neural mechanisms of addiction: The role of reward-related learning and memory

    Annu Rev Neurosci

    (2006)
  • B.J. Everitt et al.

    Neural systems of reinforcement for drug addiction: From actions to habits to compulsion

    Nat Neurosci

    (2005)
  • G. Di Chiara et al.

    Drug addiction as a disorder of associative learningRole of nucleus accumbens shell/extended amygdala dopamine

    Ann N Y Acad Sci

    (1999)
  • G.F. Koob et al.

    Drug abuse: Hedonic homeostatic dysregulation

    Science

    (1997)
  • R.L. Solomon et al.

    An opponent-process theory of motivationI. Temporal dynamics of affect

    Psychol Rev

    (1974)
  • Diagnostic and Statistical Manual of Mental Disorders. 4th ed

    (1993)
  • T.B. Baker et al.

    Addiction motivation reformulated: An affective processing model of negative reinforcement

    Psychol Rev

    (2004)
  • F.H. Gawin

    Cocaine addiction: Psychology and neurophysiology

    Science

    (1991)
  • J. Stewart et al.

    Role of unconditioned and conditioned drug effects in the self-administration of opiates and stimulants

    Psychol Rev

    (1984)
  • R.A. Wise et al.

    Both positive reinforcement and conditioned aversion from amphetamine and from apomorphine in rats

    Science

    (1976)
  • P.S. Grigson et al.

    Cocaine-induced suppression of saccharin intake: A model of drug-induced devaluation of natural rewards

    Behav Neurosci

    (2002)
  • L.A. Parker

    Rewarding drugs produce taste avoidance, but not taste aversion

    Neurosci Biobehav Rev

    (1995)
  • R.A. Wise

    Dopamine, learning and motivation

    Nat Rev Neurosci

    (2004)
  • J. Mirenowicz et al.

    Preferential activation of midbrain dopamine neurons by appetitive rather than aversive stimuli

    Nature

    (1996)
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      The headpiece was harnessed to a rotating commutator (Crist Instrument Co., Hagerstown, Maryland), and one intraoral cannula was harnessed to a fluid swivel (Instech Laboratory, Plymouth Meeting, Pennsylvania) that could receive fluid from a syringe pump (Razel, St. Albans, Vermont). On the following day, voltammetric recordings were conducted as previously described (Wheeler et al., 2011). Briefly, a carbon fiber electrode was lowered into the NAc shell, a fluid line was attached to the intraoral cannula, and the behavioral session was initiated.

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