Age and sex as vulnerability factors for methamphetamine use and its neurobehavioral consequences

Substance users who are female and begin their use during adolescence often suffer greater consequences than male and adult-onset users. Methamphetamine (METH) use may be particularly problematic given that adolescent METH users have a higher risk of relapse than adolescents who abuse other drugs, and female METH users initiate earlier than male users. The neurobehavioral mechanisms of heightened vulnerability in females and adolescent-onset METH users remain poorly understood. Although growing evidence using rodent models suggests that sex and age-of-onset are factors that confer increased susceptibility to substance use problems, there has been limited research investigating the potential interaction of these vulnerability factors. The goal of this dissertation was to further elucidate the behavioral and neural mechanisms through which age and sex may interact to confer vulnerability to developing problems with METH use. Chapter 2 investigates age and sex differences in prefrontal cortex (PFC)-sensitive behaviors that may be antecedents to substance use. Chapter 3 examines reward-taking patterns in male and female rats that began self-administration of METH or the non-drug reinforcer, saccharin, during adolescence or adulthood. The self-administration findings are extended in Chapter 4 using a model of compulsive drug-taking, and the consequences of METH use on recognition memory and receptor expression in the corticolimbic reward pathway are also examined. In Chapter 5, the role of GluN2B-containing NMDA receptor function in extinction of METH-seeking and subsequent relapse vulnerability is assessed. Results indicate that adolescents and females are hypersensitive to rewards in most contexts tested. Furthermore, adolescents may more readily develop compulsive METH-taking and PFC-sensitive cognitive dysfunction, while females may be more prone to relapse after extinction-based treatments. Taken together, the studies in this dissertation add to our current understanding of age and sex as vulnerability factors in METH use and its consequences.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Psychology

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2020

Author dc:creator

• Westbrook, Sara Ruth

Contributors dc:contributor

• Gulley, Joshua M
• Chung, Hee Jung
• Galvez, Roberto
• Juraska, Janice M
• Liang, Nu-Chu

• dopamine
• glutamate
• NMDA receptor
• adolescence
• self-administration

Statement dc:rights

• Copyright 2020 Sara Westbrook

Language dc:language

en

Handle dc:identifier

http://hdl.handle.net/2142/108607

OAI record oai:identifier

https://www.ideals.illinois.edu/oai-pmh?verb=GetRecord&metadataPrefix=etdms&identifier=oai%3Awww.ideals.illinois.edu%3A2142%2F108607