Methamphetamine facilitates female sexual behavior and enhances neuronal activation in the medial amygdala and ventromedial nucleus of the hypothalamus

Holder, Mary K.; Hadjimarkou, Maria M.; Zup, Susan L.; Blutstein, Tamara; Benham, Rebecca S.; McCarthy, Margaret M.; Mong, Jessica A.

doi:10.1016/j.psyneuen.2009.06.005

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Volume 35, Issue 2 , Pages 197-208, February 2010

Methamphetamine facilitates female sexual behavior and enhances neuronal activation in the medial amygdala and ventromedial nucleus of the hypothalamus

Mary K. Holder
- Program in Neuroscience, University of Maryland, Baltimore, School of Medicine Baltimore, MD 21201, United States
- Corresponding author at: 655 West Baltimore Street, BRB 4-002, Baltimore, MD 21201, United States. Tel.: +1 410 706 5581; fax: +1 410 706 0032.
Maria M. Hadjimarkou
- Department of Pharmacology and Experimental Therapeutics, University of Maryland, Baltimore, School of Medicine Baltimore, MD 21201, United States
- Current address: Department of Psychology, University of Cyprus, Nicosia, Cyprus.
Susan L. Zup
- Department of Physiology, University of Maryland, Baltimore, School of Medicine Baltimore, MD 21201, United States
- Current address: Department of Psychology, University of Massachusetts, Boston, Boston, MA, United States.
Tamara Blutstein
- Program in Neuroscience, University of Maryland, Baltimore, School of Medicine Baltimore, MD 21201, United States
Rebecca S. Benham
- Department of Pharmacology and Experimental Therapeutics, University of Maryland, Baltimore, School of Medicine Baltimore, MD 21201, United States
- Current address: Program in Biomedical Neurosciences, Boston University, School of Medicine, Boston, MA, United States.
Margaret M. McCarthy
- Program in Neuroscience, University of Maryland, Baltimore, School of Medicine Baltimore, MD 21201, United States
- Department of Physiology, University of Maryland, Baltimore, School of Medicine Baltimore, MD 21201, United States
Jessica A. Mong
- Program in Neuroscience, University of Maryland, Baltimore, School of Medicine Baltimore, MD 21201, United States
- Department of Pharmacology and Experimental Therapeutics, University of Maryland, Baltimore, School of Medicine Baltimore, MD 21201, United States

Received 12 March 2009; received in revised form 29 May 2009; accepted 8 June 2009.

Summary

Methamphetamine (MA) abuse has reached epidemic proportions in the United States. Users of MA report dramatic increases in sexual drive that have been associated with increased engagement in risky sexual behavior leading to higher rates of sexually transmitted diseases and unplanned pregnancies. The ability of MA to enhance sexual drive in females is enigmatic since related psychostimulants like amphetamine and cocaine appear not to affect sexual drive in women, and in rodents models, amphetamine has been reported to be inhibitory to female sexual behavior. Examination of MA's effects on female sexual behavior in an animal model is lacking. Here, using a rodent model, we have demonstrated that MA enhanced female sexual behavior. MA (5mg/kg) or saline vehicle was administered once daily for 3 days to adult ovariectomized rats primed with ovarian steroids. MA treatment significantly increased the number of proceptive events and the lordosis response compared to hormonally primed, saline controls. The effect of MA on the neural circuitry underlying the motivation for sexual behavior was examined using Fos immunoreactivity. In the medial amygdala and the ventromedial nucleus of the hypothalamus, nuclei implicated in motivated behaviors, ovarian hormones and MA independently enhance the neuronal activation, but more striking was the significantly greater activation induced by their combined administration. Increases in dopamine neurotransmission may underlie the MA/hormone mediated increase in neuronal activation. In support of this possibility, ovarian hormones significantly increased tyrosine hyroxylase (the rate limiting enzyme in dopamine synthesis) immunoreactivity in the medial amygdala. Thus our present data suggest that the interactions of MA and ovarian hormones leads to changes in the neural substrate of key nuclei involved in mediating female sexual behaviors, and these changes may underlie MA's ability to enhance these behaviors.