title: Increased functional connectivity in the resting-state basal ganglia network after acute heroin substitution.
abstract: Reinforcement signals in the striatum are known to be crucial for mediating the subjective rewarding effects of acute drug intake. It is proposed that these effects may be more involved in early phases of drug addiction, whereas negative reinforcement effects may occur more in later stages of the illness. This study used resting-state functional magnetic resonance imaging to explore whether acute heroin substitution also induced positive reinforcement effects in striatal brain regions of protracted heroin-maintained patients. Using independent component analysis and a dual regression approach, we compared resting-state functional connectivity (rsFC) strengths within the basal ganglia/limbic network across a group of heroin-dependent patients receiving both an acute infusion of heroin and placebo and 20 healthy subjects who received placebo only. Subsequent correlation analyses were performed to test whether the rsFC strength under heroin exposure correlated with the subjective rewarding effect and with plasma concentrations of heroin and its main metabolites morphine. Relative to the placebo treatment in patients, heroin significantly increased rsFC of the left putamen within the basal ganglia/limbic network, the extent of which correlated positively with patients' feelings of rush and with the plasma level of morphine. Furthermore, healthy controls revealed increased rsFC of the posterior cingulate cortex/precuneus in this network relative to the placebo treatment in patients. Our results indicate that acute heroin substitution induces a subjective rewarding effect via increased striatal connectivity in heroin-dependent patients, suggesting that positive reinforcement effects in the striatum still occur after protracted maintenance therapy.
authors: 1] Department of Psychiatry (UPK), University of Basel, Basel, Switzerland [2] Medical Image Analysis Center, University Hospital Basel, Basel, Switzerland.
authors: A
authors: A
authors: Schmidt
authors: Department of Psychiatry (UPK), University of Basel, Basel, Switzerland.
authors: N
authors: N
authors: Denier
authors: 1] Medical Image Analysis Center, University Hospital Basel, Basel, Switzerland [2] Department of Neurology, University Hospital Basel, Basel, Switzerland.
authors: S
authors: S
authors: Magon
authors: Medical Image Analysis Center, University Hospital Basel, Basel, Switzerland.
authors: E-W
authors: EW
authors: Radue
authors: Department of Psychiatry (UPK), University of Basel, Basel, Switzerland.
authors: C G
authors: CG
authors: Huber
authors: Department of Psychiatry (UPK), University of Basel, Basel, Switzerland.
authors: A
authors: A
authors: Riecher-Rossler
authors: Department of Psychiatry (UPK), University of Basel, Basel, Switzerland.
authors: G A
authors: GA
authors: Wiesbeck
authors: Department of Psychiatry (UPK), University of Basel, Basel, Switzerland.
authors: U E
authors: UE
authors: Lang
authors: 1] Department of Psychiatry (UPK), University of Basel, Basel, Switzerland [2] Medical Image Analysis Center, University Hospital Basel, Basel, Switzerland [3] Department of Psychosis Studies, Institute of Psychiatry, King's College London, London, UK.
authors: S
authors: S
authors: Borgwardt
authors: Department of Psychiatry (UPK), University of Basel, Basel, Switzerland.
authors: M
authors: M
authors: Walter
mesh_terms: D000328:Adult; D001479:Basal Ganglia / Q000187:drug effects* / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D001931:Brain Mapping / Q000379:methods; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D003932:Heroin / Q000097:blood; D006556:Heroin Dependence / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009020:Morphine / Q000097:blood; D058850:Opiate Substitution Treatment / Q000379:methods*; D012146:Rest; D012201:Reward
chemical_list: D003932:Heroin; D009020:Morphine