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.
Subject(s)
Basal Ganglia/drug effects , Basal Ganglia/metabolism , Heroin Dependence/drug therapy , Opiate Substitution Treatment/methods , Adult , Brain/drug effects , Brain/metabolism , Brain Mapping/methods , Cross-Over Studies , Double-Blind Method , Female , Heroin/blood , Heroin Dependence/blood , Humans , Magnetic Resonance Imaging , Male , Morphine/blood , Rest , RewardABSTRACT
Schizophrenia is a major mental illness that is characterized by psychosis, social withdrawal, and cognitive impairment. High comorbidity rates with substance use disorders have consistently been found - especially with abuse of cannabis and psychostimulants. While the role of these drugs in the onset of psychosis and schizophrenia has received much attention, relatively few studies have been conducted on the impact of psychoactive substances on the course of schizophrenia. In this review, study findings measuring the effects of psychoactive substances with structural and functional magnetic resonance imaging methods are described in patients suffering from substance use disorder and schizophrenia. Both Schizophrenia and substance abuse are associated with different functional brain alterations. In addicted individuals, drug-related cues and drug administration lead to increased neurofunctional activity in limbic and prefrontal brain regions compared to healthy controls. Chronic drug abuse is associated with gray matter loss in these areas. In schizophrenic patients, cognitive imaging in the frontal and temporal brain areas has showed decreased neural activity during the resting state. In chronic schizophrenic patients, the greatest loss of brain volume was found in those patients with additional substance abuse. Neuroimaging studies highlight the significance of regular drug use in schizophrenia. Whereas schizophrenic patients with and without substance abuse may not differ in structural imaging at the onset of illness, regular drug abuse seems to be a significant risk factor for severe loss of brain volume in the course of schizophrenia.