Neural responses associated with cue evoked emotional states and heroin in opiate addicts.

Ten male opiate addicts, who were current heroin injectors, underwent positron emission tomographic (PET) scanning during exposure to a sequence of six alternating drug related and neutral video cues, on two occasions. After the second scan, each subject received heroin or placebo using a randomised single-blind procedure. This design allowed the investigation of patterns of brain activity during a range of self-reported cue evoked emotional states, both in the presence and absence of heroin. Self-reports of 'urge to use' correlated strongly with increased regional blood flow (rCBF) in the inferior frontal and orbitofrontal cortex target regions of the mesolimbic dopaminergic system, implicated in conditioning and reward. 'Urge to use' was also associated with highly significant increased rCBF in the right pre-cuneus, an area associated with episodic memory retrieval, and in the left insula, implicated in the processing of the emotional components of stimuli. Self-reports of feeling 'high' correlated with rCBF activation in the hippocampus, an area relevant to the acquisition of stimulus-associated reinforcement.

Activation of reward circuitry in human opiate addicts.

The neurobiological mechanisms of opiate addictive behaviour in humans are unknown. A proposed model of addiction implicates ascending brainstem neuromodulatory systems, particularly dopamine. Using functional neuroimaging, we assessed the neural response to heroin and heroin-related cues in established opiate addicts. We show that the effect of both heroin and heroin-related visual cues are maximally expressed in the sites of origin of ascending midbrain neuromodulatory systems. These context-specific midbrain activations predict responses to salient visual cues in cortical and subcortical regions implicated in reward-related behaviour. These findings implicate common neurobiological processes underlying drug and drug-cue-related effects.

Functional magnetic resonance imaging of the acute effect of intravenous heroin administration on visual activation in long-term heroin addicts: results from a feasibility study.

This preliminary report is the first demonstration of the acute effects of diacetylmorphine (heroin) administration on functional activation in the human brain using functional magnetic resonance imaging (fMRI). Four opiate addicts who received regular prescriptions for heroin, underwent fMRI using a visual activation paradigm before and after a dose of 30 mg heroin. All four showed a decrease after the heroin dose in the extent of significant activation. This method shows promise for sequential scanning to determine brain activity in response to different drugs and routes of drug administration.

Ondansetron and opiate craving. A novel pharmacological approach to addiction.

BACKGROUND: Pharmacological approaches to opiate addiction have for the most part been limited to a role in detoxification. A high percentage of patients who complete detoxification programmes relapse. METHOD: In the present study, we used a simple laboratory method to investigate suggestions from preclinical studies that 5-(hydroxytryptamine) HT3 receptor antagonists have a role in the treatment of addiction. RESULTS: We showed that addicts stably maintained on methadone experienced significant craving, dysphoria, and withdrawal-like symptoms when exposed to a video containing drug-related cues. The craving was not lessened by treatment with the 5-HT3 receptor antagonist, ondansetron (4 mg orally). CONCLUSION: Our current findings do not support a role for 5-HT3 receptor agonists in the reduction of craving in opiate addicts.