Repeated treatment with cocaine or methamphetamine increases CRF2 and decreases astrocytic markers in the ventral tegmental area and substantia nigra

Dopamine neurons in the substantia nigra (SN) and ventral tegmental area (VTA) play a crucial role in the reinforcing properties of abused drugs including methamphetamine and cocaine. Evidence also suggests the involvement of non-dopaminergic transmitters, including glutamate and the stress-related peptide corticotropin-releasing factor (CRF), on the chronic effects of psychostimulants in the SN/VTA. Astrocytes express a variety of membrane-bound neurotransmitter receptors and transporters which influence neurotransmission in the SN/VTA. CRF2 activity in the VTA is important for stress-induced relapse and drug-seeking behavior, but the localization of its effects are not completely understood. Here we used immunofluorescence to identify the effect of methamphetamine and cocaine administration on astrocytes, the glial glutamate transporter GLAST, and CRF2 in the SN/VTA. We treated adult male mice with i.p. injections of methamphetamine (3 mg/kg), cocaine (10 mg/kg), or saline for 12 days. Coronal brain sections were processed for immunofluorescence using S100{beta} (marker for astrocytes), glial-specific glutamate/aspartate transporters (GLAST), and CRF2. The results showed a significant decrease in GLAST immunofluorescence in brains of mice treated with cocaine or methamphetamine compared to saline. In addition, we observed increased labelling of CRF2 in drug treated groups, a decrease in the number of S100{beta} positive cells, and an increase in co-staining of these two markers. Our results suggest that administration of either methamphetamine or cocaine decreases astrocytic markers and increases immunoreactivity for CRF2 in the VTA, an effect that is most pronounced in S100{beta} positive cells.