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Matthews, Marguerite (2012) CHARACTERIZING DOPAMINE FUNCTION IN ADOLESCENT RATS. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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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.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Matthews, Marguerite
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairMoghaddam, Bitabita@pitt.eduBITA
Committee MemberBradberry,
Committee MemberGrace, Anthonygraceaa@pitt.eduGRACEAA
Committee MemberMarinelli,
Committee MemberSved, Alansved@pitt.eduSVED
Committee MemberTorres, Gonzalogtorres@pitt.eduGTORRES
Date: 27 September 2012
Date Type: Publication
Defense Date: 9 July 2012
Approval Date: 27 September 2012
Submission Date: 16 August 2012
Access Restriction: 5 year -- Restrict access to University of Pittsburgh for a period of 5 years.
Number of Pages: 111
Institution: University of Pittsburgh
Schools and Programs: Dietrich School of Arts and Sciences > Neuroscience
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: adolescence, dopamine, striatum, amphetamine
Date Deposited: 28 Sep 2012 01:03
Last Modified: 27 Sep 2017 05:15


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