Nipping cue reactivity in the bud: baclofen prevents limbic activation elicited by subliminal drug cues.
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.
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.
Kimberly A
KA
Young
Teresa R
TR
Franklin
David C S
DC
Roberts
Kanchana
K
Jagannathan
Jesse J
JJ
Suh
Reagan R
RR
Wetherill
Ze
Z
Wang
Kyle M
KM
Kampman
Charles P
CP
O'Brien
Anna Rose
AR
Childress
D000293:Adolescent; D000328:Adult; D001418:Baclofen / Q000627:therapeutic use*; D019970:Cocaine-Related Disorders / Q000517:prevention & control*; D003463:Cues; D005260:Female; D058786:GABA-B Receptor Agonists / Q000627:therapeutic use*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008032:Limbic System / Q000098:blood supply / Q000187:drug effects*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010100:Oxygen / Q000097:blood; D010470:Perceptual Masking; D010775:Photic Stimulation; D011795:Surveys and Questionnaires; D055815:Young Adult
D058786:GABA-B Receptor Agonists; D001418:Baclofen; D010100:Oxygen
addiction; baclofen; cocaine; cues; fMRI; subliminal