For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
38
views
56
references
 Top references
cited by
44
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      451
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: not found

      CRF neurons in the ventral tegmental area control the aversive effects of nicotine withdrawal and promote escalation of nicotine intake

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          SUMMARY

          Dopaminergic neurons in the ventral tegmental area (VTA) are well known for their role in mediating the positive reinforcing effects of drugs of abuse. Here, we identify in rodents and humans a population of VTA dopamine neurons co-expressing corticotropin releasing factor (CRF). We provide further evidence in rodents that chronic nicotine exposure upregulates CRF mRNA in dopaminergic neurons of the posterior VTA, activates local CRF 1 receptors, and blocks nicotine-induced activation of transient GABAergic input to dopaminergic neurons. Local downregulation of CRF mRNA and specific pharmacological blockade of CRF 1 receptors in the VTA reversed the effect of nicotine on GABAergic input to dopaminergic neurons, prevented the aversive effects of nicotine withdrawal, and limited the escalation of nicotine intake. These results link the brain reward and stress systems within the same brain region in signaling the negative motivational effects of nicotine withdrawal.

          Related collections

          Most cited references56

          • Record: found
          • Abstract: found
          • Article: not found

          Addiction and the brain antireward system.

          George F Koob, Michel Le Moal (2008)
          A neurobiological model of the brain emotional systems has been proposed to explain the persistent changes in motivation that are associated with vulnerability to relapse in addiction, and this model may generalize to other psychopathology associated with dysregulated motivational systems. In this framework, addiction is conceptualized as a cycle of decreased function of brain reward systems and recruitment of antireward systems that progressively worsen, resulting in the compulsive use of drugs. Counteradaptive processes, such as opponent process, that are part of the normal homeostatic limitation of reward function fail to return within the normal homeostatic range and are hypothesized to repeatedly drive the allostatic state. Excessive drug taking thus results in not only the short-term amelioration of the reward deficit but also suppression of the antireward system. However, in the long term, there is worsening of the underlying neurochemical dysregulations that ultimately form an allostatic state (decreased dopamine and opioid peptide function, increased corticotropin-releasing factor activity). This allostatic state is hypothesized to be reflected in a chronic deviation of reward set point that is fueled not only by dysregulation of reward circuits per se but also by recruitment of brain and hormonal stress responses. Vulnerability to addiction may involve genetic comorbidity and developmental factors at the molecular, cellular, or neurocircuitry levels that sensitize the brain antireward systems.
          Article 0 comments Cited 270 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Imaging dopamine's role in drug abuse and addiction.

            N D Volkow, J Fowler, G. J. Wang … (2009)
            Dopamine is involved in drug reinforcement but its role in addiction is less clear. Here we describe PET imaging studies that investigate dopamine's involvement in drug abuse in the human brain. In humans the reinforcing effects of drugs are associated with large and fast increases in extracellular dopamine, which mimic those induced by physiological dopamine cell firing but are more intense and protracted. Since dopamine cells fire in response to salient stimuli, supraphysiological activation by drugs is experienced as highly salient (driving attention, arousal, conditioned learning and motivation) and with repeated drug use may raise the thresholds required for dopamine cell activation and signaling. Indeed, imaging studies show that drug abusers have marked decreases in dopamine D2 receptors and in dopamine release. This decrease in dopamine function is associated with reduced regional activity in orbitofrontal cortex (involved in salience attribution; its disruption results in compulsive behaviors), cingulate gyrus (involved in inhibitory control; its disruption results in impulsivity) and dorsolateral prefrontal cortex (involved in executive function; its disruption results in impaired regulation of intentional actions). In parallel, conditioning triggered by drugs leads to enhanced dopamine signaling when exposed to conditioned cues, which then drives the motivation to procure the drug in part by activation of prefrontal and striatal regions. These findings implicate deficits in dopamine activity-inked with prefrontal and striatal deregulation-in the loss of control and compulsive drug intake that results when the addicted person takes the drugs or is exposed to conditioned cues. The decreased dopamine function in addicted individuals also reduces their sensitivity to natural reinforcers. Therapeutic interventions aimed at restoring brain dopaminergic tone and activity of cortical projection regions could improve prefrontal function, enhance inhibitory control and interfere with impulsivity and compulsive drug administration while helping to motivate the addicted person to engage in non-drug related behaviors.
            Article 0 comments Cited 199 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Cellular and molecular mechanisms of drug dependence.

              G F Koob, F E Bloom (1988)
              The molecular and cellular actions of three classes of abused drugs--opiates, psychostimulants, and ethanol--are reviewed in the context of behavioral studies of drug dependence. The immediate effects of drugs are compared to those observed after long-term exposure. A neurobiological basis for drug dependence is proposed from the linkage between the cellular and behavioral effects of these drugs.
              Article 0 comments Cited 181 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Journal
                Journal ID (nlm-journal-id): 9809671
                Journal ID (pubmed-jr-id): 21092
                Journal ID (nlm-ta): Nat Neurosci
                Journal ID (iso-abbrev): Nat. Neurosci.
                Title: Nature neuroscience
                ISSN (Print): 1097-6256
                ISSN (Electronic): 1546-1726
                Publication date Nihms-submitted: 23 October 2014
                Publication date (Electronic): 17 November 2014
                Publication date (Print): December 2014
                Publication date PMC-release: 01 June 2015
                Volume: 17
                Issue: 12
                Pages: 1751-1758
                Affiliations
                [1 ]Institute of Medical Science and Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada, M5S 3E1
                [2 ]Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, California, 92037
                [3 ]Molecular and Cellular Neuroscience, The Scripps Research Institute, La Jolla, California, 92037
                [4 ]The Salk Institute, La Jolla, CA 92037
                [5 ]Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS / INSERM / Université de Strasbourg, Illkirch, F-67404, France
                [6 ]Brudnick Neuropsychiatric Research Institute, UMass Medical School 303 Belmont Street, Worcester, MA 01604
                [7 ]Douglas Hospital Research Center, Dept Psychiatry, McGill University, Montreal, H4H 1R3, Canada
                [8 ]National Institute on Alcohol Abuse and Alcoholism, Rockville, MD, 20852, USA
                Article
                Manuscript ID: NIHMS636720
                DOI: 10.1038/nn.3872
                PMC ID: 4241147
                PubMed ID: 25402857
                SO-VID: 51ddae29-90a1-4115-b953-28f0df303fb3
                History
                Categories
                Subject: Article

                ScienceOpen disciplines: Neurosciences
                Data availability:
                ScienceOpen disciplines: Neurosciences

                Comments

                Comment on this article

                scite_

                Similar content451

                See all similar

                Cited by44

                See all cited by

                Most referenced authors347

                See all reference authors