Limbic system mGluR5 availability in cocaine dependent subjects: A high-resolution PET [11C]ABP688 study

• Published in: NeuroImage (Orlando, Fla.) Vol. 98; pp. 195 - 202
• Main Authors: Milella, M.S., Marengo, L., Larcher, K., Fotros, A., Dagher, A., Rosa-Neto, P., Benkelfat, C., Leyton, M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.2014; Elsevier Limited
• Subjects: Abstinence; Addiction; Adult; Brain - diagnostic imaging; Brain - metabolism; Carbon Radioisotopes; Cocaine; Cocaine-Related Disorders - diagnostic imaging; Cocaine-Related Disorders - metabolism; Drug use; Female; Glutamate; Head injuries; Humans; Independent sample; Limbic System - diagnostic imaging; Limbic System - metabolism; Male; Oximes; Positron emission tomography; Pyridines; Receptor, Metabotropic Glutamate 5 - antagonists & inhibitors; Receptor, Metabotropic Glutamate 5 - metabolism; Relapse; Striatum; Urine; Values; Striatum; Relapse; Addiction; Glutamate; Positron emission tomography; Abstinence
• ISSN: 1053-8119; 1095-9572
• DOI: 10.1016/j.neuroimage.2014.04.061

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 [11C]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. •mGluR5 has been proposed to modulate the reinforcing properties of cocaine.•We measured mGluR5 availability in cocaine dependents using [11C]ABP688 PET ligand.•Cocaine use was associated with lower mGluR5 levels in the limbic system.•Longer abstinence from cocaine was associated with lower mGluR5 availability.•Changes in mGluR5 might reflect changes in susceptibility to drug use and relapse.