Modafinil (MOD) is an analeptic drug currently being examined as a treatment for
stimulant dependence. This experiment examined MOD’s potential for use in
treatment of methamphetamine (METH) addiction and further investigated the role
of sex differences in drug-seeking behavior and treatment receptivity. The effects
of allopregnanolone (ALLO), a progesterone metabolite that has been previously
shown to reduce drug-seeking behavior in female rats, were also examined. Rats
were trained to self-administer IV injections of METH during daily 5-hr sessions,
and continued stable METH-seeking behavior over a 10 day maintenance period.
Next, METH was replaced with saline, and drug-seeking behavior extinguished
over an 18-day period. Following extinction, rats began a reinstatement
procedure lasting 9 days in which an ALLO, MOD, or control pre-treatment
injection was given 30 minutes prior to daily session, followed by a METH or
saline priming injection that was given at the start of session. This reinstatement
phase is considered an animal model of human relapse. Females showed greater
responding on the previously METH-paired lever during reinstatement compared
to males. MOD attenuated METH-seeking behavior equally in males and females,
while MOD priming injections did not increase responding compared to saline
control. ALLO attenuated METH-seeking behavior in females, but had no effect
on males. These results illustrate the potential utility of MOD as a treatment for
METH addiction and illustrate the role of gonadal hormones, such as ALLO, in the
sex differences observed in drug-seeking behavior.
Additional contributors: Nathan Holtz; Justin Anker; Tom Baron; Alex Claxton; Seth Johnson; Brandon Knight; Sean Navin; Kinner Patel; Aneal Rege; Paul Reiger; Rachel Turner; Troy Velie; Natalie Zlebnik; Marilyn Carroll (faculty mentor)
This research was supported
by NIDA grants R01 DA018151S1 (TEP), R01 DA003240, R01 DA019942, K05
DA015267 (MEC), and the Undergraduate Research Opportunities Program (UROP) of the University of Minnesota.
Sex Differences and Effects of Modafinil and Allopregnanolone on a Rat Model of Methamphetamine Relapse.
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