title: Limbic system mGluR5 availability in cocaine dependent subjects: a high-resolution PET [(11)C]ABP688 study.
abstract: Cocaine self-administration decreases type 5 metabotropic glutamate receptor (mGluR5) tissue concentrations in laboratory rats during early abstinence. These changes are thought to influence the drug's reinforcing properties and the ability of drug-related cues to induce relapse. Here, our goal was to measure brain regional mGluR5 availability in recently abstinent cocaine dependent humans. Participants meeting DSM-IV diagnostic criteria for current cocaine dependence (n=9) were recruited from the general population. mGluR5 availability (binding potential, non-displaceable; BPND) was measured with high-resolution positron emission tomography (PET HRRT) and [(11)C]ABP688. Compared to age- and sex-matched healthy controls (n=9), cocaine dependent subjects showed significantly lower BPND values in the ventral (bilateral: -28.2%, p=0.011), associative (right: -21.4%, p=0.043), and sensorimotor striatum (bilateral: -21.7%, p=0.045), amygdala (left: -26%, p=0.046) and insula (right: -23.3%, p=0.041). Among the cocaine users, receptor availabilities were related to abstinence (range: 2 to 14days). The longer the duration of abstinence, the lower the BPND values in the sensorimotor striatum (r=-0.71, p=0.034), left amygdala (r=-0.73, p=0.026) and right insula (r=-0.67, p=0.046). Compared to healthy controls, BPND values were significantly reduced in those who tested negative for cocaine on the PET test session in the ventral (p=0.018) and sensorimotor striatum (p=0.017), left amygdala (p=0.008), and right insula (p=0.029), but not in those who tested positive. Together, these results provide evidence of time-related mGluR5 alterations in striatal and limbic regions in humans during early cocaine abstinence.
authors.affiliation: Department of Psychiatry, McGill University, Montreal H3A 1A1, Canada.
authors.forename: M S
authors.initials: MS
authors.lastname: Milella
authors.affiliation: Department of Psychiatry, McGill University, Montreal H3A 1A1, Canada.
authors.forename: L
authors.initials: L
authors.lastname: Marengo
authors.affiliation: Department of Neurology & Neurosurgery, Montreal Neurological Institute, McGill University, Montreal H3A 2B4, Canada.
authors.forename: K
authors.initials: K
authors.lastname: Larcher
authors.affiliation: Department of Psychiatry, McGill University, Montreal H3A 1A1, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Fotros
authors.affiliation: Department of Neurology & Neurosurgery, Montreal Neurological Institute, McGill University, Montreal H3A 2B4, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Dagher
authors.affiliation: Translational Neuroimaging Laboratory, Douglas Research Institute, Montreal H4H 1R3, Canada.
authors.forename: P
authors.initials: P
authors.lastname: Rosa-Neto
authors.affiliation: Department of Psychiatry, McGill University, Montreal H3A 1A1, Canada; Department of Neurology & Neurosurgery, Montreal Neurological Institute, McGill University, Montreal H3A 2B4, Canada.
authors.forename: C
authors.initials: C
authors.lastname: Benkelfat
authors.affiliation: Department of Psychiatry, McGill University, Montreal H3A 1A1, Canada; Department of Neurology & Neurosurgery, Montreal Neurological Institute, McGill University, Montreal H3A 2B4, Canada; Center for Studies in Behavioral Neurobiology, Concordia University, Montreal H4B 1R6, Canada. Electronic address: marco.leyton@mcgill.ca.
authors.forename: M
authors.initials: M
authors.lastname: Leyton
mesh_terms: D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D002250:Carbon Radioisotopes; D019970:Cocaine-Related Disorders / Q000000981:diagnostic imaging / Q000378:metabolism*; D005260:Female; D006801:Humans; D008032:Limbic System / Q000000981:diagnostic imaging / Q000378:metabolism*; D008297:Male; D010091:Oximes; D049268:Positron-Emission Tomography; D011725:Pyridines; D064529:Receptor, Metabotropic Glutamate 5 / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: C510950:3-(6-methylpyridin-2-ylethynyl)cyclohex-2-enone-O-methyloxime; D002250:Carbon Radioisotopes; C578935:GRM5 protein, human; D010091:Oximes; D011725:Pyridines; D064529:Receptor, Metabotropic Glutamate 5
keywords: Abstinence; Addiction; Glutamate; Positron emission tomography; Relapse; Striatum