1,721,166 research outputs found
Molecular mechanisms of cannabinoid addiction
No full textCannabis is the world's most widely used illicit substance, with an estimated number of 119–224 million users worldwide. In recent years we assisted to an increased effort aimed to individuate the brain circuits underlying cannabis addiction and dependence. Similarly to other drugs of abuse, repeated exposure to cannabinoids causes brain neuroadaptations that persist long after drug effects, contribute to the negative affective states during withdrawal, and ultimately facilitate relapse. Recently, considerable progress has been made in understanding the cellular and molecular consequences of prolonged cannabis use, among which is the identification of specific set of transcriptional regulations that develop differently after chronic cannabinoids and in the abstinent brain
The Roman high- and low-avoidance rat lines differ in the acquisition, maintenance, extinction, and reinstatement of intravenous cocaine self-administration
No full textNeuropsychopharmacology. 2009 Apr;34(5):1091-101. Epub 2008 Apr 16.
The Roman high- and low-avoidance rat lines differ in the acquisition,
maintenance, extinction, and reinstatement of intravenous cocaine
self-administration.
Fattore L, Piras G, Corda MG, Giorgi O.
Institute of Neuroscience CNR, Section of Cagliari, Italy.
The selective breeding of Roman high- (RHA) and low-avoidance (RLA) rats for,
respectively, rapid vs extremely poor acquisition of avoidant behavior in a
shuttlebox has produced two phenotypes that differ in temperament traits, in
mesocortical/mesolimbic dopamine system function, and in the behavioral and
neurochemical responses to the acute and repeated administration of
psychostimulants and opiates. The phenotypic traits of the RHA line predict
higher susceptibility, compared with RLA rats, to the reinforcing properties of
addictive substances like cocaine. The present study was designed to compare the
acquisition, maintenance, reinstatement of drug-seeking after long-term
extinction, and reacquisition of intravenous cocaine self-administration (SA)
behavior in the Roman lines. Compared with RLA rats, the rates of responding
during cocaine SA acquisition were higher, extinction from cocaine SA was
prolonged, and drug-induced reinstatement of cocaine-seeking behavior was more
robust in RHA rats. Moreover, only RHA rats reacquired extinguished
lever-pressing activity when a low reinforcing dose of cocaine was available.
These findings are consistent with the view that subjects with genetically
determined high responsiveness to the acute and chronic (ie, sensitizing) effects
of psychostimulants, such as RHA rats, also display a higher propensity to self
-administer cocaine. Further comparative studies in the Roman lines, using SA
paradigms that distinguish mere drug-taking from the compulsive and uncontrolled
drug use that characterizes addiction in humans, may eventually help to
characterize the relationships among genotype, temperament traits, and
neurobiological mechanisms involved in the individual vulnerability to cocaine
addiction.
PMID: 18418365 [PubMed - indexed for MEDLINE
Drug addiction: An affective-cognitive disorder in need of a cure
No full textDrug addiction is a compulsive behavioral abnormality. In spite of pharmacological treatments and psychosocial support to reduce or eliminate drug intake, addiction tends to persist over time. Preclinical and human observations have converged on the hypothesis that addiction represents the pathological deterioration of neural processes that normally serve affective and cognitive functioning. The major elements of persistent compulsive drug use are hypothesized to be structural, cellular and molecular that underlie enduring changes in several forebrain circuits that receive input from midbrain dopamine neurons and are involved in affective (e.g. ventral striatum) and cognitive (e.g. prefrontal cortex) mechanisms. Here we review recent progress in identifying crucial elements useful to understand the pathophysiology of the disease and its treatments. Manipulation of neuropeptides brain systems and pharmacological targeting of κ-opioid receptors and/or drug metabolism may hold beneficial effects at affective and cognitive level. Non-pharmacological, highly innovative approaches such as Transcranial Magnetic Stimulation may reveal unsuspected potential and promise to be the first neurobiology-based therapeutics in addiction
Cannabinoid modulation of emotion, memory, and motivation
No full textThe endocannabinoid system consists of cannabinoid receptors, their endogenous lipid ligands (endocannabinoids) and the enzymatic machinery for their synthesis and degradation. In the brain, endocannabinoids regulate ion channel activity and neurotransmitter release and thereby contribute to various aspects of brain function, including memory, reward and emotions. Their ability to modulate synaptic efficacy has a wide range of functional consequences and provides unique therapeutic possibilities. Unprecedented advances have been made in the understanding of the role of endocannabinoids in the regulation of the emotional brain over the past few years. However, a comprehensive book encompassing all these aspects is still lacking. The book will provide an overview of the role played by the endocannabinoid system in the regulation of emotional processes with particular emphasis on the modulation of memory and reward for emotionally arousing events and for the regulation of motivational aspects in cannabis use
Reinstatement of opioid-seeking by cannabinoids in animal models of relapse to drug abuse
No full textRevised Scaled-Size Prototype Design
No full textNST 224 Politecnico di Torino - HELINET Reports N. HE-087A1A-POL-RP-04. Issued 18/12/2000. 20 Pages
Endocannabinoid regulation of relapse mechanisms
No full textAddiction involves a complex neuropharmacologic behavioural cycle, in which positive reinforcement exerted by the drug and the negative state of withdrawal drive the user to extremes to obtain the drug. Comprehensive studies have established that relapse is the most common outcome of recovery programs treating addictive behaviours. Several types of anticraving medication are available nowadays, such as naltrexone for the treatment of alcoholism, bupropion for nicotine, methadone or buprenorphine for heroin. This review focuses on recent behavioural data providing a rationale for an endocannabinoid mechanism underlying reinstatement of compulsive drug seeking. Studies supporting the contention that reinstatement of extinguished drug self-administration behaviour may be generated by cannabinoid CB I receptor agonists and attenuated, if not blocked. by CB I receptor antagonists, are here reviewed. In support to these findings, conditioned place preference studies substantiate the involvement of the endocannabinoid system in recidivism mechanisms by demonstrating that motivation to relapse can be triggered by CB I receptor activation while blockade of such receptors may prevent reinstatement of place conditioning induced by either drug primings or drug-associated cues. Finally biochemical studies evaluating changes in endocannabinoid levels, CB I receptor density and CB I mRNA expression during re-exposure to drug following extinction are also examined. Taken together, the evidence available has important implications in the understanding and treatment of relapsing episodes in patients undergoing detoxification
Therapeutic Use of Synthetic Cannabinoids: Still an Open Issue?
No full textCannabis sativa has a long history of use for medical purposes despite marijuana's addictive potential. The discovery of the endogenous cannabinoid system as a neuromodulatory system composed of receptors, endogenous ligands (endocannabinoids), and enzymes responsible for their synthesis and degradation, together with recent advancements in the elucidation of cannabinoid pharmacology, has renewed interest in medicines acting on the endocannabinoid system. Synthetic cannabinoid agonists have been developed and used for treatment of different human pathologic conditions, and promising potent cannabinoid antagonists are currently under clinical evaluation. During the last decade, new generations of synthetic cannabinoids appeared on the global drug market, proposed as marijuana-like compounds and sold as herbal mixture also known as spice drugs or legal highs. Because activation of cannabinoid receptors may induce central and peripheral beneficial effects, the newest synthetic cannabinoids having full agonistic activity and high potency at cannabinoid type 1 and type 2 receptors might have therapeutic potential too. However, case reports of acute and fatal intoxications are accumulating and revealing that this is not the case because adverse effects of the latest generation of synthetic cannabinoids far exceed the desired ones
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