Year: 2012
Type: article
Abstract: Adolescence is a developmental period that coincides with increased exploration, social interaction, risk-taking, and novelty-seeking, as well as the symptomatic onset of psychiatric illnesses. Remodeling of the mesocorticolimbic and nigrostriatal dopamine systems has been implicated in these vulnerabilities. Yet, little is known about functional consequences of this remodeling. This dissertation sought to investigate the dynamics of dopamine neurotransmission in adolescent rats in two functionally distinct dopamine innervated striatal subregions: the nucleus accumbens (NAc), which is implicated in reward processing, and the dorsal striatum (DS), which is involved in habit formation and flexible learning. The psychostimulant amphetamine was used as a tool to activate dopamine release in behaving rats. Microdialysis was used to measure extracellular levels of dopamine. An acute systemic administration of amphetamine caused smaller amphetamine-induced dopamine efflux in the DS of adolescent rats (postnatal days 35-38) compared to adults. Dopamine in NAc was increased similarly in both age groups. Amphetamine also caused reduced levels of stereotypy behavior in adolescents than adults. Reduced effectiveness of amphetamine in DS was not due to age-related differences in the dopamine transporter (DAT). Though adolescents have lower levels of DAT in the NAc and DS than adults, the DAT inhibitor nomifensine similarly inhibited basal and amphetamine-induced dopamine efflux in both striatal subregions of both age groups. Furthermore, vesicular monoamine transporter-2 (VMAT2) expression was similar in the DS and NAc of both adolescent and adult rats. In contrast, expression of tyrosine hydroxylase (TH) was reduced in the DS, but not the NAc, of adolescents compared to adults. The adolescent rats also were behaviorally more sensitive to the effects of a TH inhibitor. Together these data suggest that dopamine neurotransmission in the DS of adolescents is hypofunctional compared to adults, resulting in part from reduced TH activity. Given that actions of dopamine on striatal neurons are primarily inhibitory, functions associated with DS, such as action selection and habit formation, may be less responsive to dopamine meditated inhibition during adolescence.
Author: Marguerite Matthews
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W629876333