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Brief Communications

Nipping Cue Reactivity in the Bud: Baclofen Prevents Limbic Activation Elicited by Subliminal Drug Cues

Kimberly A. Young, Teresa R. Franklin, David C.S. Roberts, Kanchana Jagannathan, Jesse J. Suh, Reagan R. Wetherill, Ze Wang, Kyle M. Kampman, Charles P. O'Brien and Anna Rose Childress
Journal of Neuroscience 2 April 2014, 34 (14) 5038-5043; DOI: https://doi.org/10.1523/JNEUROSCI.4977-13.2014
Kimberly A. Young
1Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104,
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Teresa R. Franklin
1Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104,
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David C.S. Roberts
2Department of Physiology and Pharmacology, School of Medicine, Wake Forest University, Winston-Salem, North Carolina 27157, and
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Kanchana Jagannathan
1Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104,
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Jesse J. Suh
1Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104,
3Philadelphia VA Medical Center, Philadelphia, Pennsylvania 19104
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Reagan R. Wetherill
1Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104,
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Ze Wang
1Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104,
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Kyle M. Kampman
1Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104,
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Charles P. O'Brien
1Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104,
3Philadelphia VA Medical Center, Philadelphia, Pennsylvania 19104
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Anna Rose Childress
1Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104,
3Philadelphia VA Medical Center, Philadelphia, Pennsylvania 19104
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Abstract

Relapse is a widely recognized and difficult to treat feature of the addictions. Substantial evidence implicates cue-triggered activation of the mesolimbic dopamine system as an important contributing factor. Even drug cues presented outside of conscious awareness (i.e., subliminally) produce robust activation within this circuitry, indicating the sensitivity and vulnerability of the brain to potentially problematic reward signals. Because pharmacological agents that prevent these early cue-induced responses could play an important role in relapse prevention, we examined whether baclofen—a GABAB receptor agonist that reduces mesolimbic dopamine release and conditioned drug responses in laboratory animals—could inhibit mesolimbic activation elicited by subliminal cocaine cues in cocaine-dependent individuals. Twenty cocaine-dependent participants were randomized to receive baclofen (60 mg/d; 20 mg t.i.d.) or placebo. Event-related BOLD fMRI and a backward-masking paradigm were used to examine the effects of baclofen on subliminal cocaine (vs neutral) cues. Sexual and aversive cues were included to examine specificity. We observed that baclofen-treated participants displayed significantly less activation in response to subliminal cocaine (vs neutral) cues, but not sexual or aversive (vs neutral) cues, than placebo-treated participants in a large interconnected bilateral cluster spanning the ventral striatum, ventral pallidum, amygdala, midbrain, and orbitofrontal cortex (voxel threshold p < 0.005; cluster corrected at p < 0.05). These results suggest that baclofen may inhibit the earliest type of drug cue-induced motivational processing—that which occurs outside of awareness—before it evolves into a less manageable state.

  • addiction
  • baclofen
  • cocaine
  • cues
  • fMRI
  • subliminal
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The Journal of Neuroscience: 34 (14)
Journal of Neuroscience
Vol. 34, Issue 14
2 Apr 2014
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Nipping Cue Reactivity in the Bud: Baclofen Prevents Limbic Activation Elicited by Subliminal Drug Cues
Kimberly A. Young, Teresa R. Franklin, David C.S. Roberts, Kanchana Jagannathan, Jesse J. Suh, Reagan R. Wetherill, Ze Wang, Kyle M. Kampman, Charles P. O'Brien, Anna Rose Childress
Journal of Neuroscience 2 April 2014, 34 (14) 5038-5043; DOI: 10.1523/JNEUROSCI.4977-13.2014

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Nipping Cue Reactivity in the Bud: Baclofen Prevents Limbic Activation Elicited by Subliminal Drug Cues
Kimberly A. Young, Teresa R. Franklin, David C.S. Roberts, Kanchana Jagannathan, Jesse J. Suh, Reagan R. Wetherill, Ze Wang, Kyle M. Kampman, Charles P. O'Brien, Anna Rose Childress
Journal of Neuroscience 2 April 2014, 34 (14) 5038-5043; DOI: 10.1523/JNEUROSCI.4977-13.2014
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Keywords

  • addiction
  • baclofen
  • cocaine
  • cues
  • fMRI
  • subliminal

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  • Implications for Treatment of Cocaine Addiction
    M. Saad Khan
    Published on: 19 February 2016
  • Published on: (19 February 2016)
    Page navigation anchor for Implications for Treatment of Cocaine Addiction
    Implications for Treatment of Cocaine Addiction
    • M. Saad Khan, Student

    The research presented here demonstrates a truly novel approach to the treatment of cocaine addiction. More recent literature indicates activation associated with the limbic system in response to drug cues (Childress et al., 2015). Comprehensive literature searches indicate that, to date, there has not been any significant advancement in this regard. Treatment via drugs such as Baclofen remains an area of untapped potent...

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    The research presented here demonstrates a truly novel approach to the treatment of cocaine addiction. More recent literature indicates activation associated with the limbic system in response to drug cues (Childress et al., 2015). Comprehensive literature searches indicate that, to date, there has not been any significant advancement in this regard. Treatment via drugs such as Baclofen remains an area of untapped potential.

    While there is no doubt that the prevention of subliminal drug cues will play an instrumental role in the prevention of relapse in the future, would not the actual onset of these cues be virtually unknown to the individual him/herself? There continues to be a glaring paucity of research in this area. While conscious drug cues themselves are considered subjective in nature, cues of a subconscious nature will consequently be of a more controversial nature when treatment options are being considered. Among the findings mentioned in the paper, the authors conceded the possibility of Baclofen exerting more generalized effects on motivational processes, considering its role as a dopamine modulator. As a result, its role in pharmacotherapy becomes immediately questionable - would the advantages of using such a drug to treat essentially undetectable subliminal cues override the risk associated with generalized effects on motivational responses that extend to other facets of life? The practicality of using this drug so comes into question - how would clinicians be aware of the presence of subliminal drug cues so as to justify the use of Baclofen for treatment? The obvious answer is to use neuroimaging measures, such as fMRI. But would this be effective in the treatment of addiction when large populations are considered? Considering the number of addicted individuals in the present day, subjecting individuals who have been treated for cocaine addiction to fMRI tests at regular intervals seems like a sensible strategy, but definitely not cost-effective in the long-term.

    The question I posit here by no means seeks to undermine the novel findings presented by the authors. As I mentioned earlier, the findings demonstrate a significant area of untapped potential when it comes to the treatment of cocaine addiction (and potentially addiction to other drugs). Indeed, there have been findings for Baclofen's usefulness in the treatment of alcohol dependence and comorbid anxiety (Morley et al., 2014), although, in this instance, the findings were quite selective to the specific condition of alcohol dependence and comorbid anxiety. This therefore highlights the need for more research with this specific focus.

    Conflict of Interest:

    None declared

    Show Less
    Competing Interests: None declared.

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