RT Journal Article
SR Electronic
T1 Nipping Cue Reactivity in the Bud: Baclofen Prevents Limbic Activation Elicited by Subliminal Drug Cues
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 5038
OP 5043
DO 10.1523/JNEUROSCI.4977-13.2014
VO 34
IS 14
A1 Kimberly A. Young
A1 Teresa R. Franklin
A1 David C.S. Roberts
A1 Kanchana Jagannathan
A1 Jesse J. Suh
A1 Reagan R. Wetherill
A1 Ze Wang
A1 Kyle M. Kampman
A1 Charles P. O'Brien
A1 Anna Rose Childress
YR 2014
UL http://www.jneurosci.org/content/34/14/5038.abstract
AB 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.