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

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 14 days). 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.