Nicotine- and Cocaine-triggered Methamphetamine Reinstatement in Female and Male Sprague-Dawley Rats

Preclinical studies have demonstrated a return to methamphetamine (meth)-seeking behavior (reinstatement) induced by injections of meth administered by the experimenter (drug-prime). Notably, females tend to be more sensitive to drug-prime; often displaying more reinstatement behavior when compared to males. While meth-primed reinstatement of meth-seeking behavior has been established, little is known about the ability of other drugs of abuse to substitute for meth during drug-primed reinstatement; nicotine and cocaine were the focus of the present work. We also examined if self-administration and/or reinstated meth-seeking behavior was affected by repeated nicotine administration. Male and female Sprague-Dawley rats were trained to self-administer meth during daily sessions. During this self-administration phase, rats were placed into 1 of 2 groups: saline or repeated nicotine exposure. Rats in the repeated nicotine group received nicotine injections 4h after meth self-administration sessions, whereas the remaining rats received saline. Following self-administration was extinction in which meth was no longer available and nicotine was no longer administered. After extinction, rats were tested to determine if 0 (saline), 0.2, and 0.4mg/kg nicotine reinstated meth-seeking behavior. Three days of re-extinction followed nicotine testing. Finally, rats received reinstatement tests with 0 (saline), 5, and 10mg/kg cocaine. Nicotine and cocaine reinstated meth-seeking behavior in male and female rats with no difference between the sexes. Repeated nicotine administration potentiated meth reinstatement following the 0.4mg/kg nicotine-prime. While females may be more sensitive to reinstatement triggered with the original self-administration drug, this effect may not generalize to priming with other drugs of abuse.