Methamphetamine enhances sexual behavior in female rats

Abstract

The present study evaluated the effects of methamphetamine (MA) on sexual behavior in female rats. In Experiment 1, ovariectomized, hormone-primed rats were injected with MA (1.0 mg/kg, i.p.) or saline prior to a test for mate choice wherein females could mate with two males simultaneously. Female rats treated with saline returned to their preferred mate faster after receiving intromissions and visited their preferred mate at a higher rate than their non-preferred mate. In contrast, MA-treated female rats spent a similar amount of time with their preferred and non-preferred mate and failed to return to their preferred mate faster than to their non-preferred mate following intromissions. Two weeks later, the females received the same drug treatment but were tested for partner preference wherein females could spend time near a male or female stimulus rat. All subjects spent more time near the male stimulus than the female stimulus. However, the MA-treated rats visited the male stimulus more frequently and spent less time near the female stimulus than the saline-treated rats. Similar to Experiment 1, female rats in Experiment 2 were tested for mate choice and then two weeks later tested for partner preference; however, females received three daily injections of MA (1.0 mg/kg, i.p.) or saline. Females treated chronically with MA returned to both males faster following intromissions than females treated with saline, independent of preference (i.e., preferred mate and non-preferred mate). Furthermore, MA-treated rats were more likely to leave either male (i.e., preferred or non-preferred mate) than saline-treated rats after receiving sexual stimulation. Although MA-treated subjects spent more time near the male stimulus than the female stimulus, they spent less time near either when compared to saline-treated subjects. The present results demonstrate that MA affects sexual behavior in female rats partly by increasing locomotion and partly by directly affecting sexual behavior.

Introduction

Methamphetamine (MA) is a commonly abused psychomotor stimulant (Darke et al., 2008). Use of MA has increased over the last decade—in both the number of users (Lorvick et al., 2006, Semple et al., 2004a) and the diversity of user-demographics (Brecht et al., 2005). For example, MA is now one of the most common drugs used by high school students and is widely available in urban, suburban, and rural communities across the United States (Maxwell, 2005, Springer et al., 2007). Unlike other psychomotor stimulants, MA is purported to have robust and distinct effects on sexual behavior (Leavitt, 1969, Rawson et al., 2002). Some MA users take MA to enhance sexual pleasure (Semple et al., 2004a). Specifically, while under the influence of MA, users report experiencing enhanced sexual pleasure, enhanced sexual confidence, and enhanced sexual performance compared to when they are not using MA (Semple et al., 2004a, Semple et al., 2004b). In addition, MA users are also more likely to engage in sexual risk taking than non-drug users (Semple et al., 2004a, Semple et al., 2004b). For example, individuals who use MA (including male heterosexual, male homosexual, and female heterosexual users) are more likely to report having participated in anal intercourse and having more sexual partners within the previous 12-month period than non-drug users (Molitor et al., 1998, Molitor et al., 1999). The use of MA is also associated with low rates of condom usage (Semple et al., 2004a, Semple et al., 2004b) and high rates of prostitution (Molitor et al., 1998, Molitor et al., 1999). As a potential consequence of engaging in high-risk sexual behavior, MA users are more likely to have contracted a sexually transmitted infection in their lifetime than non-drug users (Lorvick et al., 2006, Molitor et al., 1998, Molitor et al., 1999, Semple et al., 2004a, Semple et al., 2004b). Finally, one study (Lorvick et al., 2006) compared women who inject MA regularly to women who inject other drugs of abuse, such as heroin. Lorvick et al. (2006) found that women who inject MA were more likely to report having unprotected anal intercourse, having sex for money or drugs, and having more than five sexual partners within the previous six month period than women who inject other drugs.

Although the findings from surveys of drug users suggest a relationship between sexual behavior and MA use, few empirical studies have investigated the effects of MA (in animals or humans) on female sexual behavior. Sexual motivation can be studied using animal models, such as rats in laboratory settings (Guarraci, 2010). During mating, female rats display a number of complex behavioral patterns that allow them to control their sexual interactions with male rats [reviewed in (Erskine, 1989)]. For example, a female rat will mate with multiple males simultaneously and pace the receipt of sexual stimulation by retreating from the males between sexual contacts (Calhoun, 1948, Calhoun, 1962, McClintock and Adler, 1977, McClintock et al., 1982, Robitaille and Bovet, 1976). The female rat's ability to control the number and timing of her sexual contacts by approaching and withdrawing from a male (known as paced-mating behavior) (McClintock and Adler, 1977) ensures optimal fertility for the female (Coopersmith and Erskine, 1994, Erskine et al., 1989). When female rats are given the opportunity to pace the receipt of sexual stimulation from two or more males simultaneously, they will display a preference for one male over another by spending more time with him and returning to him more quickly after receiving sexual stimulation (Lovell et al., 2007). A female rat's preference for a particular male is consistent across repeated encounters with the same pair of males (i.e., preferring the same male 70% of the time). Female rats also display solicitation behaviors (i.e., hopping, darting, presenting and ear wiggling), which “solicit” the attention of male partners, and indicate a female rat's motivation to mate (Beach, 1976, Erskine, 1989). Together, the ability to control the temporal pattern of mating with multiple males, the display of solicitation behaviors and the expression of the lordosis reflex represent the full repertoire of mating behavior in the female rat (Beach, 1976, Erskine, 1989).

One empirical study, which investigated the effects of MA administration on sexual behavior in female rats, found that repeated MA administration increased receptive (i.e., the lordosis reflex) and solicitation behaviors (Holder et al., 2009). However, this study did not measure female sexual motivation in a paradigm that allows a female rat to control her interaction with multiple potential sexual partners simultaneously. The present study was designed to investigate the effects of acute and chronic MA administration on several different aspects of female sexual behavior by using both a mate choice test as well as a partner preference paradigm in order to gain insight into the potential for MA to enhance sexual motivation. The mate choice test, wherein a female mates with two males simultaneously, allows for the expression of a preference for one male over another. The partner preference paradigm allows for the expression of a sexual preference over a social preference.