Extended Amygdala to Ventral Tegmental Area Corticotropin-Releasing Factor Circuit Controls Binge Ethanol Intake.

BACKGROUND

Corticotropin-releasing factor (CRF) signaling at the CRF receptor (CRFR) in the ventral tegmental area (VTA) can modulate ethanol consumption in rodents. However, the effects of binge-like ethanol drinking on this system have not been thoroughly characterized, and little is known about the role of CRFR or the CRF neurocircuitry involved.

METHODS

The effects of binge-like ethanol consumption on the VTA CRF system were assessed following drinking-in-the-dark procedures. Intra-VTA infusions of selective CRFR and/or CRFR compounds were employed to assess the contributions of these receptors in modulating binge-like ethanol consumption (n = 89). To determine the potential role of CRF projections from the bed nucleus of the stria terminalis (BNST) to the VTA, CRF neurons in this circuit were chemogenetically inhibited (n = 32). Binge-induced changes in VTA CRF system protein and messenger RNA were also assessed (n = 58).

RESULTS

Intra-VTA antagonism of CRFR and activation of CRFR resulted in decreased ethanol intake, which was eliminated by simultaneous blockade of both receptors. Chemogenetic inhibition of local CRF neurons in the VTA did not alter binge-like ethanol drinking, but inhibition of VTA-projecting CRF neurons from the BNST significantly reduced intake.

CONCLUSIONS

We provide novel evidence that 1) blunted binge-like ethanol consumption stemming from CRFR blockade requires intact CRFR signaling, and CRFR activation reduces binge-like drinking; 2) inhibiting VTA-projecting BNST CRF neurons attenuates binge-like drinking; and 3) binge-like ethanol drinking alters protein and messenger RNA associated with the VTA-CRF system. These data suggest that ethanol-induced activation of BNST-to-VTA CRF projections is critical in driving binge-like ethanol intake.