Stress-Induced Dopamine Release in mPFC: An 18F-Fallypride / PET Study in Healthy Volunteers

Abstract

Background: In rats, stressful stimuli are known to activate dopamine projections to the limbic/paralimbic systems, including the medial prefrontal cortex (mPFC), resulting into marked and transient dopamine (DA) release. In humans, acute stress has been associated with DA release in the striatum in PET studies, although the radioligand used (11C-Raclopride) precluded an examination of extra-striatal DA pathways.

Methods: PET and [18F]-Fallypride were used to measure the impact of an anxiety provoking ¬¬challenge in the laboratory (MIST), on dopamine release in cortical, subcortical, and limbic/paralimbic areas. Nine healthy male volunteers (age; 20.6+/-2.6) completed two PET measurements on separate days (stress and non-stress sessions). We used a Neuroticism index (NEO) to measure individual anxiety-proneness. Heart rate and skin conductance were collected at regular intervals during the scans. Individual binding potential maps were created for stress and non-stress sessions, and stress induced DA release was calculated based on GLM and ROI analyses.

Results: As expected, the response to the MIST, relative to the non-stress condition, resulted in a significant increase in heart rate and skin conductance (paired t-test: t=4.66, p≤0.01, t=2.96, p≤0.05). Stress-induced DA release was observed in the mPFC and dorsal anterior cingulate cortex (dACC) (t=6.0; x =-8, y=22, z=42). Inverse correlations between neuroticism scores, the change in skin conductance, respectively, and stress-induced DA release in mPFC, was noted (r= -0.88, p≤0.01; r=-.0.84, p≤0.01).

Conclusions: In healthy volunteers, acute social stress may result in dopamine release in the mPFC/dACC. Paradoxically, anxiety-prone individuals may have an attenuated stress-induced DA release response.