Year: 2020
Type: dissertation
Abstract: Neurobiological adaptations in the nucleus accumbens (NAc) following withdrawal from drug use are associated with vulnerability to relapse. Among the identified changes in the NAc is decreased expression of the glutamate transporter GLT-1. Because GLT-1 is primarily expressed on astrocytes, an important and related question emerges regarding what other adaptations occur in astrocytes subsequent to drug use. Recent studies indicate that short-access cocaine self-administration and extinction training in rats leads to a decrease in the surface area, volume, and synaptic colocalization of NAc astrocytes. However, it is currently unknown if these findings extend to other rodent models of cocaine self-administration. Moreover, it is unknown whether these findings extend to female rats. Therefore, the goals of the dissertation were to examine the effects of long-access (LgA) cocaine self-administration and prolonged abstinence on (1) NAc GLT-1 expression in female rats and (2) the structural plasticity of NAc astrocytes in both sexes. Finally, a third goal of this dissertation was to examine if changes in NAc GLT-1 expression and NAc astrocytes are correlational or mechanistically linked. The experiments described in Chapter 2 revealed that GLT-1 mRNA and protein levels are unchanged in the NAc of female rats, despite the fact that both are decreased in males. The experiments described in Chapter 3 showed that although astrocytes from male rats exhibited a decrease in surface area, volume, and synaptic colocalization, these changes were not observed in female rats. Finally, the experiments described in Chapter 4 showed that although GLT-1 overexpression in the NAc had no effect on the cocaine-induced decrease in the surface area and volume of astrocytes, it significantly increased synaptic colocalization. The results from Chapter 4 also showed that NAc GLT-1 overexpression had no effect on the incubation of cocaine craving. Collectively, these data suggest sex differences in GLT-1 expression, as well as in the changes in NAc astrocytes following LgA cocaine self-administration and abstinence. These results also show that the downregulation in GLT-1 expression and the cocaine-induced changes in NAc astrocytes are not mechanistically linked, and further, that GLT-1 overexpression alone is not sufficient to attenuate cocaine seeking.
DOI: 10.17615/bt65-sr36
Author: Kim, Ronald
Institution: University of North Carolina at Chapel Hill
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W3216749825