Nipping cue reactivity in the bud: baclofen prevents limbic activation elicited
by subliminal drug cues.
Author(s): Young KA(1), Franklin TR, Roberts DC, Jagannathan K, Suh JJ, Wetherill RR, Wang
Z, Kampman KM, O'Brien CP, Childress AR.
Affiliation(s): Author information:
(1)Department of Psychiatry, Perelman School of Medicine, University of
Pennsylvania, Philadelphia, Pennsylvania 19104, Department of Physiology and
Pharmacology, School of Medicine, Wake Forest University, Winston-Salem, North
Carolina 27157, and Philadelphia VA Medical Center, Philadelphia, Pennsylvania
19104.
Publication date & source: 2014, J Neurosci. , 34(14):5038-43
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.
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