Nucleus accumbens AGS3 expression drives ethanol seeking through Gβγ
Abstract
Approximately 90% of alcoholics relapse within 4 years, in part because of an enhanced motivation to seek alcohol (EtOH). A novel G protein modulator (Gpsm1/AGS3) was up-regulated in the rat nucleus accumbens core (NAcore) but not in other limbic nuclei during abstinence from operant EtOH self-administration. Furthermore, NAcore AGS3 knockdown reduced EtOH seeking to pre-abstinence levels in a novel rat model of compulsive, human EtOH seeking. AGS3 can both inhibit G protein Giα-mediated signaling and stimulate Gβγ-mediated signaling. Accordingly, sequestration of Gβγ, but not Giα knockdown, significantly reduced EtOH seeking to pre-abstinence levels. Thus, AGS3 and Gβγ are hypothesized to gate the uncontrolled motivation to seek EtOH during abstinence. AGS3 up-regulation during abstinence may be a key determinant of the transition from social consumption to compulsion-like seeking during relapse.
- Publication:
-
Proceedings of the National Academy of Science
- Pub Date:
- August 2008
- DOI:
- 10.1073/pnas.0706999105
- Bibcode:
- 2008PNAS..10512533B
- Keywords:
-
- self-administration;
- reinstatement;
- alcohol deprivation effect;
- Giα
- G protein;
- Biological Sciences:Neuroscience