Behavioral and neurochemical effects of 96-hour methamphetamine self-administration in male and female rats: Creating, developing and characterizing a novel model of methamphetamine abuse

Methamphetamine is a highly addictive psychostimulant drug of abuse for which no FDA approved treatment exists. Methamphetamine is unique among psychostimulants in that its use is associated with increases in violence, aggression, aberrant sexual behavior and HIV/AIDS. In the past 25 years, there has been a dramatic increase in methamphetamine use in the United States, predominantly among women. However, female subjects are understudied compared to males. Women tend to initiate methamphetamine use earlier than men and prefer to use methamphetamine over other drugs. Furthermore, women are considered to be significantly more violent under the influence of methamphetamine compared to men; violence which is not reported with the use of other drugs of abuse. Women methamphetamine users are typically of childbearing age and there is a large repertoire of police reports stating that under the influence of methamphetamine, women abuse, neglect, torture and murder their children. While high on methamphetamine, both male and female methamphetamine users report engaging in risky (i.e. unprotected, with strangers, with multiple partners at once) sexual behavior and are more likely to be involved in violent criminal activities, engage in domestic violence and sexual violence. Since methamphetamine administration can involve needles for injection and increased violent and risky sexual behavior, this drug poses as a significant risk factor for the spread of HIV/AIDS. All of these factors contribute to the dangerous reputation associated with methamphetamine, thus, developing a useful treatment to combat methamphetamine addiction is necessary. Humans typically use methamphetamine in a binge and crash, meaning they take the drug for days at a time (binge) and then abruptly stop taking the drug (crash) until they can acquire more. I have recently developed a 96-hour methamphetamine self-administration model in rats, which may more closely resemble how human methamphetamine users take the drug. The focus of my dissertation was to utilize this 96-hour model to assess drug-taking behaviors, aggressive behavior and neurochemical and physiological alterations induced by methamphetamine taking in male and female rats. The objective of my dissertation was to validate this novel model of methamphetamine self-administration by exploring behaviors and neurobiology involved in methamphetamine addiction in male and female rats in a way that I believe is more translatable to the human condition of methamphetamine taking. The 96-hour methamphetamine self-administration model itself is considered a correlative model, which has predictive validity. The aggressive behaviors as well as methamphetamine-induced neurobiological and physiological changes in these rats are considered to be isomorphic and homologous models that have face and construct validity, as human methamphetamine addicts display aggressive behaviors and the neurobiology and physiology underlying these behaviors is similar between rats and humans. My central hypothesis is that chronic 96-hour methamphetamine self-administration In male and female rats leads to the development of behavioral, neurochemical and physiological alterations that are also present in human methamphetamine users..