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