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Abstract
Methamphetamine (meth) dependence is often characterized by persistent and chronic relapse (i.e., return to drug use). There is growing pre-clinical and human evidence suggesting females are at greater risk to relapse. The set of studies presented in this dissertation extended this limited evidence by identifying sex-dependent neural substrates correlated with meth-triggered reinstatement (Experiment 1) and by examining sex-differences in reinstatement triggered by drugs of abuse that are commonly co-abused with meth (Experiment 2). Female and male rats were trained to self-administer meth, received subsequent extinction sessions, and then tested for reinstatement. In Experiment 1, rats were perfused following reinstatement testing and c-Fos activity was examined as a measure of neural activation. Meth triggered reinstatement in both sexes and this effect was more robust in females compared to males. In the females, c-Fos activity was significantly increased following meth-primed reinstatement in the cingulate cortex area 1, lateral orbitofrontal cortex, prelimbic cortex, caudate-putamen, nucleus accumbens core and shell, and central nucleus of the amygdala. In males, there were no significant differences following meth-primed reinstatement. In Experiment 2, nicotine and cocaine were utilized as drug primes to determine if administration of these drugs could trigger meth-seeking behavior. Nicotine and cocaine reinstated meth-seeking behavior in male and female rats with no difference between the sexes. Females were more sensitive to reinstatement triggered with the original self-administration drug and this effect may not generalize to priming with other drugs of abuse.
