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Examination of methamphetamine reinstatement in female and male rats: A pre-clinical model of relapse

Steven T Pittenger, University of Nebraska - Lincoln


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.

Subject Area


Recommended Citation

Pittenger, Steven T, "Examination of methamphetamine reinstatement in female and male rats: A pre-clinical model of relapse" (2016). ETD collection for University of Nebraska-Lincoln. AAI10142449.