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Reinstatement of methamphetamine seeking in male and female rats treated with modafinil and allopregnanolone
Holtz, Nathan A. Lozama, Anthony Prisinzano, Thomas E. Carroll, Marilyn E.
Holtz, Nathan A.
Lozama, Anthony
Prisinzano, Thomas E.
Carroll, Marilyn E.
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Abstract
Background
Sex differences in methamphetamine (METH) use (females>males) have been demonstrated in clinical and preclinical studies. This experiment investigated the effect of sex on the reinstatement of METH-seeking behavior in rats and to determine whether pharmacological interventions for METH-seeking behavior vary by sex. Treatment drugs were modafinil (MOD), an analeptic, and allopregnanolone (ALLO), a neuroactive steroid and progesterone metabolite.
Method
Male and female rats were trained to self-administer i.v. infusions of METH (0.05mg/kg/infusion). Next, rats self-administered METH for a 10-day maintenance period. METH was then replaced with saline, and rats extinguished lever-pressing behavior over 18 days. A multi-component reinstatement procedure followed where priming injections of METH (1 mg/kg) were administered at the start of each daily session, preceded 30 min by MOD (128 mg/kg, i.p.), ALLO (15 mg/kg, s.c.), or vehicle treatment. MOD was also administered at the onset of the session to determine if it would induce the reinstatement of METH-seeking behavior.
Results
Female rats had greater METH-induced reinstatement responding compared to male rats following control treatment injections. MOD (compared to the DMSO control) attenuated METH-seeking behavior in male and female rats; however, ALLO only reduced METH-primed responding in females. MOD alone did not induce the reinstatement of METH-seeking behavior.
Conclusions
These results support previous findings that females are more susceptible to stimulant abuse compared to males and ALLO effectively reduced METH-primed reinstatement in females. Further, they illustrate the utility of MOD as a potential agent for prevention of relapse to METH use in both males and females.
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Date
2013-01-01
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Elsevier
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Keywords
Allopregnanolone, Methamphetamine, Modafinil, Rats, Reinstatement, Sex differences
Citation
Holtz, Nathan A., Anthony Lozama, Thomas E. Prisinzano, and Marilyn E. Carroll. "Reinstatement of Methamphetamine Seeking in Male and Female Rats Treated with Modafinil and Allopregnanolone." Drug and Alcohol Dependence 120.1-3 (2012): 233-37.