Astrocytic hypertrophy in the rat ventral tegmental area following chronic morphine differs with age

J Neurol Neurorehabilit Res. 2018;3(1):14-21.


The ventral tegmental area (VTA) is the origin of the mesolimbic dopaminergic system known to play an integral role in mediating reward and development of drug addiction. Although the differences in neuronal plasticity of VTA at various ages remain to be understood, age is known to influence the effects of chronic opioids. In addition, adaptations associated with exposure to opioids within glial populations located in the VTA are poorly understood. The objective of the study was to determine if there are changes in astrocytic immunofluorescent labeling in the VTA following chronic morphine administration in a rat model at different ages: newborn at postnatal day (PD)7 and adult (estimated PD57). We hypothesized that increased immunohistochemical labeling of an astrocytic marker, glial fibrillary acidic protein (GFAP) in the VTA following chronic administration of morphine will not differ with age. Two groups of rats were analyzed: chronic morphine and saline control treatment groups. Either morphine (10 mg/kg) or equal volume of saline was given subcutaneously twice daily for 6½ days. On the 7th day of treatment, animals were anesthetized and perfused at one hour after the final drug injection. Coronal sections of the midbrain were processed for immunofluorescent identification of GFAP that was noted at both ages. We report an increase in both (1) GFAP labeling intensity, as well as (2) the percent area occupied by astrocytes that are immunoreactive for GFAP following chronic morphine when compared to saline treatment in the VTA only for the adults (n=6/group) but not infant rats at PD7 (n=5/group). Our findings suggest that adaptations in the mesolimbic dopaminergic system produced by repeated exposure to opioids may be associated with changes in glial function that differ with age.

Keywords: Addiction; Astrocytes; GFAP; Glial Activation; Neuroinflammation; Tolerance.