Methamphetamine and cocaine administration increases CRF‐R2 and decreases S100‐beta astrocytic immunoreactivity in the VTA

Abstract

Dopamine neurons in the ventral tegmental area (VTA) play a crucial role in the reinforcing properties of abused drugs including methamphetamine and cocaine. However, there is evidence suggesting the involvement of non‐dopaminergic transmitters, including glutamate and corticotropin‐releasing factor (CRF), on psychostimulant effects in the VTA. Astrocytes can express a large variety of receptors for neurotransmitters such as glutamate which could indirectly influence neurotransmission in the VTA. Additionally, corticotropin‐releasing factor (CRF) receptors have been reported on astrocytes in the cerebellum, although no one has yet identified them on astrocytes in the VTA. CRF in the VTA plays a role in stress‐induced relapse and drug‐seeking behavior, but the localization of its effects are not completely understood. Although tissue from mouse VTA shows a high level of CRF1 receptor transcript and lower levels of CRF2 receptor transcript, both receptors play a functional role in regulating VTA synaptic activity.Here, we aimed to use immunofluorescence to identify the effect of methamphetamine and cocaine administration on astrocytic glutamate and CRF receptors. We treated adult male mice with i.p. injections of methamphetamine (3 mg/kg), cocaine (10 mg/kg), or saline (vehicle) for 12 days. Brains were then removed and sectioned (40 μm thickness) in the coronal plane. The tissue was then processed for immunofluorescence using tyrosine hydroxylase as a dopaminergic cell marker and S100‐beta as a marker for astrocytes. We examined the level of glutamate and glutamate/aspartate transporters (GLT‐1 and GLAST) and CRF receptors. Images were captured using fluorescent microscopy and processed using ImageJ software. The results showed a ~30% decrease in GLT‐1 and GLAST immunofluorescence in brains of mice treated with cocaine or methamphetamine compared to saline. In addition, we observed increased labelling of CRF2 receptors in drug‐treated groups, a decrease of S100beta, and an increase of co‐staining of these markers. Our results suggest that administration of either methamphetamine or cocaine increases immunoreactivity for CRF2 receptors in the VTA, an effect that is most pronounced in S100‐ beta positive cells.Support or Funding InformationThis work was supported by National Institute on Aging grant R01 AG052606.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.