Methamphetamine-induced neuroadaptations in the rat: Effects of adolescent use on the dopaminergic system and drug taking behaviors

Carrica, Lauren Katherine

Permalink

https://hdl.handle.net/2142/127265 Copy

Description

Title

Methamphetamine-induced neuroadaptations in the rat: Effects of adolescent use on the dopaminergic system and drug taking behaviors

Author(s)

Carrica, Lauren Katherine

Issue Date

2024-12-04

Director of Research (if dissertation) or Advisor (if thesis)

Gulley, Joshua M

Doctoral Committee Chair(s)

Gulley, Joshua M

Committee Member(s)

• Juraska, Janice M
• Liang, Nu-Chu
• Hinman, James R
• Antonson, Adrienne M

Department of Study

Psychology

Discipline

Psychology

Degree Granting Institution

University of Illinois at Urbana-Champaign

Degree Name

Ph.D.

Degree Level

Dissertation

Keyword(s)

• methamphetamine
• adolescence
• dopamine
• catechol-o-methyltransferase
• COMT
• rodent
• amphetamines

Abstract

Individuals who initiate methamphetamine (METH) use during adolescence are at a greater risk of developing a substance use disorder (SUD) than those who initiate as adults, potentially due to unique impacts of the drug upon the developing brain. In particular, METH’s ability to increase synaptic concentrations of dopamine in regions like the prefrontal cortex (PFC) may disrupt the normal maturation of inhibitory function, which is facilitated by dopamine. Despite evidence that exposure to METH alters dopamine transporter (DAT) expression, little is known about how METH impacts expression of catechol-o-methyltransferase (COMT): the primary mechanism of dopamine clearance within the PFC. The goal of this dissertation was to increase our understanding of the mechanisms by which dopamine clearance is disrupted by METH exposure, and how these alterations may differ by sex and age of exposure. The work described in Chapter 2 establishes the ontogeny of COMT within the PFC and nucleus accumbens (NAc) across specific time points within adolescence in rats of both sexes. In Chapter 3, we examine the effects of METH exposure on parvalbumin (PV) inhibitory interneurons within these same windows, and the experiment in Chapter 4 expands upon these findings to investigate METH’s effects on COMT expression in the PFC. Finally, in Chapter 5 we investigate the long-term effects of METH exposure during adolescence on later drug-taking behavior in female rats. Our results indicate that COMT changes across adolescence in a sex-specific way, and that METH uniquely impacts both PV and COMT in post-pubertal adolescent females compared to adults. Furthermore, METH exposure during adolescence leads to rapid escalation of METH intake during self-administration in adulthood. Together, the studies in this dissertation highlight the sex- and age-specific effects of METH exposure, and reveal COMT alterations as a potential mechanism by which METH leads to long-lasting changes in drug taking behaviors which may underlie increased vulnerability to developing SUDs.

Graduation Semester

2024-12

Type of Resource

Thesis

Handle URL

https://hdl.handle.net/2142/127265

Copyright and License Information

Copyright 2024 Lauren Carrica

Owning Collections