Enhanced c-Fos in periaqueductal grey GABAergic neurons during opioid withdrawal.

The ventrolateral subdivision of periaqueductal grey is crucial for expression of opioid withdrawal signs. Previous investigations suggest that interneurons rather than the medullary projecting output neurons in this midbrain region are hyperexcited during opioid withdrawal. In the present study, transgenic mice with glutamic acid decarboxylase-containing neurons coupled to enhanced green fluorescent protein expression were used as a marker for GABAergic neurons and for studying opioid withdrawal. We found that these transgenic mice exhibited a full range of opioid withdrawal signs on abrupt cessation of chronic opioid action. Consistent with previous studies, c-Fos expression was also robustly enhanced (two-fold) in the ventrolateral periaqueductal grey. Furthermore, about one third (30%) of glutamic acid decarboxylase-containing neurons coupled to enhanced green fluorescent protein in the ventrolateral periaqueductal grey were stained c-Fos positive (i.e. a four-fold increase from control mice). These results indicate hyperexcitation of GABAergic neurons in the ventrolateral periaqueductal grey during opioid withdrawal.