heroin and Memory-Disorders

Addiction is a chronic disorder involving recurring intoxication, withdrawal, and craving episodes. Escaping this vicious cycle requires maintenance of abstinence for extended periods of time and is a true challenge for addicted individuals. The emergence of depressive symptoms, including social withdrawal, is considered a main cause for relapse, but underlying mechanisms are poorly understood. Here we establish a mouse model of protracted abstinence to heroin, a major abused opiate, where both emotional and working memory deficits unfold. We show that delta and kappa opioid receptor (DOR and KOR, respectively) knockout mice develop either stronger or reduced emotional disruption during heroin abstinence, establishing DOR and KOR activities as protective and vulnerability factors, respectively, that regulate the severity of abstinence. Further, we found that chronic treatment with the antidepressant drug fluoxetine prevents emergence of low sociability, with no impact on the working memory deficit, implicating serotonergic mechanisms predominantly in emotional aspects of abstinence symptoms. Finally, targeting the main serotonergic brain structure, we show that gene knockout of mu opioid receptors (MORs) in the dorsal raphe nucleus (DRN) before heroin exposure abolishes the development of social withdrawal. This is the first result demonstrating that intermittent chronic MOR activation at the level of DRN represents an essential mechanism contributing to low sociability during protracted heroin abstinence. Altogether, our findings reveal crucial and distinct roles for all three opioid receptors in the development of emotional alterations that follow a history of heroin exposure and open the way towards understanding opioid system-mediated serotonin homeostasis in heroin abuse.

Topics: Animals; Antidepressive Agents, Second-Generation; Depression; Disease Models, Animal; Dorsal Raphe Nucleus; Fluoxetine; Heroin; Heroin Dependence; Male; Memory Disorders; Memory, Short-Term; Mice, 129 Strain; Mice, Inbred C57BL; Mice, Knockout; Narcotics; Receptors, Opioid, kappa; Receptors, Opioid, mu; Social Behavior; Spatial Memory; Substance Withdrawal Syndrome

Topics: Administration, Inhalation; Ataxia; Brain; Brain Damage, Chronic; Heroin; Heroin Dependence; Humans; Magnetic Resonance Imaging; Male; Memory Disorders; Middle Aged; Narcotics; Nerve Fibers, Myelinated; Neurotoxicity Syndromes; Reflex, Abnormal

The case is described of a patient who, following cerebral hypoxia, developed severe difficulty in orienting himself in new environments in the context of a mild global amnesic syndrome. Some episodes he related suggested that his main difficulty was remembering the spatial/directional value of landmarks he recognised. A neuroradiological examination documented severe bilateral atrophy of the hippocampi associated with atrophic changes in the cerebral hemispheres, most marked in the dorsal regions. Neuropsychological and experimental evaluation showed a severe deficit of spatial learning with substantially preserved ability to learn verbal and visual-object information. He was also virtually unable to learn a route in a maze task based exclusively on spatial data, but the availability of visual cues substantially improved his learning. Finally, he performed within normal limits on various tests investigating knowledge acquired premorbidly regarding famous buildings, routes in the town he had been living in since childhood, and geography. Topographical disorientation may be subtended by a specific difficulty in storing the spatial/directional value of visual landmarks in novel environments. The hippocampus appears to be involved in the acquisition of new topographical spatial knowledge.

Topics: Adult; Amnesia, Anterograde; Confusion; Frontal Lobe; Heroin; Hippocampus; Humans; Hypoxia, Brain; Illicit Drugs; Magnetic Resonance Imaging; Male; Maze Learning; Memory Disorders; Narcotics; Neuropsychological Tests; Orientation; Parietal Lobe; Temporal Lobe

A 43-year-old woman developed acute paraplegia and a Korsakoff syndrome following intravenous administration of heroin. Thirteen previously reported cases are similar to the one presented here. Based on those similarities, we conclude that these myelopathies are probably due to spinal cord infarction resulting from systemic hypoxemia and hypotension.

Topics: Adult; Female; Heroin; Humans; Memory Disorders; Paraplegia; Substance Abuse, Intravenous