Prepubescent Electronic Cigarette Exposure Affects Sexual Motivation and Puberty in Female But Not Male Long-Evans Rats.

INTRODUCTION: A method for delivering vaporized nicotine to animals has been developed using e-cigarette devices. The present experiment was designed to measure the effects of e-cigarette nicotine on pubertal onset and development of reproductive behavior in female and male Long-Evans rats. AIM AND METHODS: Rats received daily 10-min sessions of electronic-cigarette vaporized nicotine (5% Virginia Tobacco JUUL Pods) or room air in a whole-body exposure chamber (postnatal day 28-31). Pubertal onset was monitored daily (ie, vaginal opening in females, preputial separation in males). Two weeks later, rats were tested for sexual motivation using the partner-preference paradigm, whereby subjects were given the opportunity to approach either a sexual partner or a same-sex social partner. Four weeks later, partner preference was assessed again, 10 min after rats were re-exposed to their same prepubertal treatment. RESULTS: We found that prepubescent electronic-cigarette vaporized nicotine disrupted puberty and sexual motivation in female but not male rats. In vaped females, vaginal opening was delayed and less time was spent with the male stimulus compared to room-air controls. In contrast, no effect of e-cigarette vapor was observed on pubertal onset or on any measures of sexual behavior in male rats. No effects were observed in either female or male rats on the second partner-preference test. CONCLUSIONS: Prepubescent vaporized nicotine affected the development of reproductive physiology and behavior in female rats but not in male rats, whereas an additional acute exposure to nicotine vapor had no effect in either female or male adult rats. IMPLICATIONS: Given the prevalence of increasingly younger users, more animal research is needed to explore the effects of e-cigarette smoking on multiple developmental systems including reproductive physiology and behavior. This model could be useful in exploring multiple behavioral and physiological endpoints in both sexes. Adjustments to the duration of exposure and control conditions will be necessary for future experiments to best model human use.

Daily GnRH agonist treatment delays the development of reproductive physiology and behavior in male rats.

The present study was designed to examine the effects of suppressing pubertal onset with leuprolide acetate, a gonadotropin releasing hormone (GnRH) agonist. Starting on postnatal day (PD) 25, male Long-Evans rats were injected daily with either leuprolide acetate (25 µg/kg dissolved in 0.9% sterile physiological saline; n = 13) or sterile physiological saline (1.0 ml/kg 0.9% NaCl; n = 14) for a total of 25 days. Males were monitored daily for signs of puberty (i.e., preputial separation). On the last day of leuprolide treatment (PD 50), half of each treatment group was injected with 10.0 µg of estradiol benzoate (EB) daily for three consecutive days (PD 50-52) and 1.0 mg of progesterone (P) on the 4th day (PD 53), whereas the other half of each treatment group received oil injections. Four hours after P injections, all subjects were given the opportunity to interact with a gonadally-intact male and a sexually receptive female rat (i.e., a partner-preference test with and without physical contact). Copulatory behavior and sexual motivation were measured. Hormone injections and mating tests were repeated weekly for a total of 3 consecutive weeks. Results showed that leuprolide delayed puberty as well as the development of copulatory behavior and the expression of sexual motivation. By the last test, the leuprolide-treated subjects showed signs of catching up, however, many continued to be delayed. Estradiol and progesterone mildly feminized male physiology (e.g., decreased testes weight and serum testosterone) and behavior (e.g., increased lordosis), but did not interact with leuprolide treatment.

Neonatal exposure to genistein affects reproductive physiology and behavior in female and male Long-Evans rats.

The present study was designed to examine the effects of neonatal genistein exposure on measures of reproductive physiology and behavior. Approximately 24 h after birth, female and male Long-Evans rat pups were injected daily with genistein (150 µg, subcutaneous; n = 29) or olive oil (n = 23) between postnatal days 1 and 5. After weaning, we examined all subjects daily until they reached puberty (i.e. vaginal opening in female rats and preputial separation in male rats). For all female subjects, we also examined vaginal cytology. After monitoring estrous cyclicity, the female subjects were given the opportunity to interact with a gonadally intact male or a sexually receptive female rat on the day of behavioral estrus to assess sexual motivation (i.e. partner-preference test with and without physical contact), which has never been evaluated before. For all male subjects, we assessed the development of copulatory behavior and sexual motivation (partner-preference test without physical contact). Consistent with previous findings, we found that neonatal exposure to genistein did not affect puberty onset in female or male rats. However, female rats exposed to genistein displayed significantly more irregular estrous cycles than controls. Neonatal genistein exposure also altered the development of male copulatory behavior, as indicated by an increase in mount frequency and intromission frequency and shorter interintromission intervals. We extended previous findings confirming that neither female nor male sexual motivation was affected by neonatal genistein. The results of the present study have important implications for the development of reproductive physiology and behavior in human neonates exposed to genistein in soy-based baby formula.

Age and Long-Term Hormone Treatment Effects on the Ultrastructural Morphology of the Median Eminence of Female Rhesus Macaques.

The median eminence (ME) of the hypothalamus comprises the hypothalamic nerve terminals, glia (especially tanycytes) and the portal capillary vasculature that transports hypothalamic neurohormones to the anterior pituitary gland. The ultrastructure of the ME is dynamically regulated by hormones and undergoes organizational changes during development and reproductive cycles in adult females, but relatively little is known about the ME during aging, especially in nonhuman primates. Therefore, we used a novel transmission scanning electron microscopy technique to examine the cytoarchitecture of the ME of young and aged female rhesus macaques in a preclinical monkey model of menopausal hormone treatments. Rhesus macaques were ovariectomized and treated for 2 years with vehicle, estradiol (E2), or estradiol + progesterone (E2 + P4). While the overall cytoarchitecture of the ME underwent relatively few changes with age and hormones, changes to some features of neural and glial components near the portal capillaries were observed. Specifically, large neuroterminal size was greater in aged compared to young adult animals, an effect that was mitigated or reversed by E2 alone but not by E2 + P4 treatment. Overall glial size and the density and tissue fraction of the largest subset of glia were greater in aged monkeys, and in some cases reversed by E2 treatment. Mitochondrial size was decreased by E2, but not E2 + P4, only in aged macaques. These results contrast substantially with work in rodents, suggesting that the ME of aging macaques is less vulnerable to age-related disorganization, and that the effects of E2 on monkeys' ME are age specific.

Methamphetamine induces DNA damage in specific regions of the female rat brain.

Methamphetamine (METH) is a highly addictive psychostimulant that has been shown to produce neurotoxicity. Methamphetamine increases the release of dopamine by reversing the direction of monoamine transporter proteins, leading to the formation of reactive oxygen species in the brain. In this study, we examined the effect of METH on DNA damage in vivo using the single cell gel electrophoresis assay (comet assay) under two different conditions. Rats treated with multiple doses of METH (10 mg/kg × 4) showed significant levels of DNA damage in the nucleus accumbens and striatum, both dopamine-rich areas. In contrast, a single dose of METH did not lead to significant levels of DNA damage in any of the dopamine-rich brain regions that were tested. Overall, the results of our study demonstrate that METH produces greater oxidative DNA damage in brain areas that receive greater dopamine innervation.

Sexual attractiveness in male rats is associated with greater concentration of major urinary proteins.

Female rats show a distinct attraction for males. This attraction remains consistent without the necessity for the physical presence of the male. However, the identity of the olfactory cues contributing to attraction in rats remains unknown. Rat urine contains copious amounts of major urinary proteins (MUPs). Here, we investigated the hypothesis that MUPs mediate sexual attractiveness in rats. We first demonstrated that a member of a male dyad receiving greater copulatory opportunities in competitive mate choice tests excrete greater amounts of MUPs. Furthermore, the amount of male MUPs positively correlated with both copulatory opportunities received and female exploration of the urine. Using females and a two-choice olfactory attraction test, we demonstrated that urinary fractions containing MUPs were sufficient to induce attraction and that male MUPs activated neurons in the posterodorsal medial amygdala in female rats. Taken together, these results suggest that olfactory cues associated with MUPs act as an attractant to female rats in estrus.

Chronic periadolescent leuprolide exposure affects the development of reproductive physiology and behavior of female and male rats differently, but both mature after treatment termination.

BACKGROUND: GnRH agonists have been used to halt the development of puberty in children with precocious puberty since the 1980s. Recently, drugs like Lupron Depot® (leuprolide acetate), have been used to suppress pubertal progression in adolescents who are questioning their gender identity. However, few preclinical studies have been conducted to investigate potential effects of using GnRH agonists in this context. METHODS: The present study tested the effects of daily leuprolide treatment (50 µg/kg, postnatal day (PD) 25-50) on pubertal onset in female (i.e., vaginal opening) and male (i.e., preputial separation) Long-Evans rats. The first estrous cycle immediately after vaginal opening was also measured. Sexual behavior and sexual motivation were tested using the partner-preference paradigm. Female rats were tested during the first behavioral estrus after treatment ended (between PD 51-64). Male rats were tested weekly for four consecutive weeks starting three days after treatment ended (PD 53). RESULTS: Consistent with previous findings, leuprolide significantly delayed pubertal onset in both female and male rats. In addition, the first estrous cycle during the treatment period was disrupted by leuprolide, as indicated by a failure to cycle into estrus after vaginal opening until treatment ended. However, leuprolide affected neither sexual motivation nor fertility when female rats were tested within 14 days of leuprolide treatment ending. In contrast, the development of copulatory behavior and sexual motivation was significantly delayed by leuprolide in male rats; however, mature reproductive behavior was observed by the fourth week post-treatment. CONCLUSIONS: Taken together with previous findings, the present results indicate that male rats may be more sensitive to periadolescent leuprolide administration, taking longer to overcome the effects of leuprolide than female rats. Nevertheless, not long after leuprolide treatment is discontinued, sex-typical reproductive physiology and behavior emerge fully in female and male rats, indicating that the drug's effects are not permanent. If translatable to humans, leuprolide may be a reversible option to give adolescents more time to consider their gender identity with minimal long-term effects on sexual development.

Daily GnRH agonist treatment effectively delayed puberty in female rats without long-term effects on sexual behavior or estrous cyclicity.

The present study examined the long-term effects of suppressing puberty with a GnRH agonist on reproductive physiology and behavior in female rats. We have recently reported that administration of the GnRH agonist leuprolide acetate (25 µg/kg) daily between postnatal day (PD) 25-50 delayed puberty and disrupted the development of copulatory behavior and sexual motivation in male rats. However, pilot data from our lab suggest that this low dose of leuprolide acetate (25 µg/kg) was not high enough to significantly delay puberty in female rats. Therefore, we injected female Long-Evans rats with leuprolide acetate at a higher dose (50 µg/kg) or 0.9% sterile saline, daily , starting on PD 25 and ending on PD 50. Vaginal opening was monitored daily starting on PD 30 for signs of pubertal onset and first estrous cycle. In addition, we measured estrous cyclicity starting approximately 2 weeks after the last injection of leuprolide (∼PD 64). Immediately after monitoring estrous cyclicity, the female rats were mated on their first day in behavioral estrus using the partner-preference paradigm, with and without physical contact (PD 95-110). We found that this dose of leuprolide (50 µg/kg) significantly delayed puberty; however, neither estrous cyclicity nor sexual motivation was significantly affected by periadolescent exposure to leuprolide. Together with our findings in male rats, these results add to our understanding of the developmental effects of chemically suppressing puberty in rats.

Male rat sexual behavior: Insights from inter-copulatory intervals.

The assessment of sexual behavior in male rats with the aim of unraveling underlying neurobiological mechanisms has in the recent decades been reduced to the annotation of mounts, intromissions and ejaculations. To provide a better understanding of the structure and patterns of copulation, it is necessary to extend and tailor the analysis to the natural organization of male rat copulation. This will lead to better formulation of hypotheses about neurobiological underpinnings of behavior. Mounts and intromissions are naturally organized in mount bouts consisting of one or more copulatory behaviors and are interspersed with time outs. We hypothesized that time outs and the post-ejaculatory interval (inter-copulatory intervals) are related and possibly under the control of a common copulatory inhibition mechanism that is the result of penile sensory stimulation. To test this hypothesis, we analyzed sexual behavior in male rats of three different cohorts from three different laboratories. Results showed that the post-ejaculatory interval and mean time out duration are strongly correlated in all cohorts analyzed. In addition, we showed that individual time out duration is at least partially predicted by the sum of sensory stimulation of copulatory components in the preceding mount bout, with more penile stimulation associated with longer time outs. These findings suggest that both time out and post-ejaculatory interval duration may be determined by the magnitude of sensory stimulation, which inhibits copulation. Whether the same neural pathways are involved in the central orchestration of both time outs and the post-ejaculatory interval should be subject to future studies.

"Sex, drugs and the brain": the interaction between drugs of abuse and sexual behavior in the female rat.

Preclinical and clinical research investigating female sexual motivation has lagged behind research on male sexual function. The present review summarizes recent advances in our understanding of the specific roles of various brain areas, as well as our understanding of the role of dopaminergic neurotransmission in sexual motivation of the female rat. A number of behavioral paradigms that can be used to thoroughly evaluate sexual behavior in the female rat are first discussed. Although traditional assessment of the reflexive, lordosis posture has been useful in understanding the neuroanatomical and neurochemical systems that contribute to copulatory behavior, the additional behavioral paradigms described in this review have helped us expand our understanding of appetitive and consumatory behavioral patterns that better assess sexual motivation - the equivalent of "desire" in humans. A summary of numerous lesion studies indicates that different areas of the brain, including forebrain and midbrain structures, work together to produce the complex repertoire of female sexual behavior. In addition, by investigating the effects of commonly addictive drugs, we are beginning to elucidate the role of dopaminergic neurotransmission in female sexual motivation. Consequently, research in this area may contribute to meaningful advances in the treatment of human female sexual dysfunction.

II. Antidepressants and sexual behavior: Acute fluoxetine, but not ketamine, disrupts paced mating behavior in sexually experienced female rats.

Female sexual dysfunction is both a symptom of depression and exacerbated by treatments for depression. Ketamine, a novel treatment for depression, has been shown to enhance, whereas fluoxetine has been shown to impair sexual motivation. Sexual experience leads to more robust partner preference and paced mating behavior in female rats. Whether acute ketamine and fluoxetine similarly affect sexual motivation and mating behavior in sexually experienced female rats is unknown. Sexually experienced female rats received 10 mg/kg i.p. of ketamine or saline vehicle (Experiment 1) or 10 mg/kg i.p. of fluoxetine or water vehicle (Experiment 2) 30 min before a 10-min no-contact partner preference test followed immediately by a 15-intromission paced mating test. Partner preference and paced mating behavior did not differ between ketamine- and saline-treated rats. In contrast, rats treated with fluoxetine spent significantly less time with either stimulus animal and were less active during the partner preference test than water-treated rats. Additionally, contact-return latency to ejaculation was significantly longer in fluoxetine-treated rats and they spent less time with the male during paced mating in comparison to water-treated rats. Thus, even with sexual experience, fluoxetine disrupts sexual function whereas ketamine has no detrimental effects on sexual behavior in female rats. A growing body of evidence suggests that ketamine is an encouraging new approach to treat depression particularly because it is not associated with sexual dysfunction.

Modified limited bedding and nesting is a model of early-life stress that affects reproductive physiology and behavior in female and male Long-Evans rats.

We used a modification of the limited bedding and nesting (LBN) model to evaluate the effects of early-life stress (ELS) on female and male reproductive physiology and behavior in Long-Evans rats. On postnatal day (PD) 2, dams and pups were transferred to a cage containing 100 mL of bedding (LBN condition) or to a cage containing 500 mL of bedding (control condition); bedding conditions remained until PD 10. In female rats, we measured vaginal opening, estrous cyclicity, female sexual behavior and motivation, and anxiety-like behavior. In male rats, we measured preputial separation, the development of male copulatory behavior, sexual motivation, and anxiety-like behavior. We found that relative to controls, female rats reared with LBN experienced precocious puberty and enhanced sexual motivation, but normal estrous cyclicity. Relative to controls, male rats reared with LBN experienced delayed puberty and enhanced sexual motivation, but normal development of copulatory behavior. Anxiety-like behavior was not affected by LBN in either female or male rats. In summary, the ELS of being reared with LBN affected the onset of puberty in the opposite direction in females and males, but enhanced sexual motivation in both. The current study is the first to examine the effects of ELS on sexual motivation using the LBN model. These findings further support the hypothesis that maternal care affects the development of sexual maturation and sexual motivation.

Sexual Behavior is Enhanced by Regular, Repeated Mating from Young Adulthood to Middle Age in Female Long-Evans Rats.

BACKGROUND: Aging is associated neuroendocrine changes in women. Animals can be used to model these changes, as well as changes in reproductive behavior. OBJECTIVE: The current study was designed to characterize mating behavior across age and assess the effects of age and sexual history on mating behavior. METHODS: Sexual motivation was assessed using the partner-preference test, in which a female rat is given the choice to interact with a same-sex conspecific or a sexually-vigorous male rat, with which she can mate. RESULTS: Across repeated mating tests (2-12 months of age), female rats spent more time with the male, displayed more solicitation behaviors, were less likely to leave the male after mounts, but visited both stimulus animals less frequently. Comparing a separate group of age-matched, hormoneyoked female rats mated for the first time at 12 months of age to female rats mated for the first time at 2 months of age showed that the 12 month rats visited both stimulus animals less, were less likely to leave the male after mounts, took longer to return to the male after mounts, and displayed fewer solicitation behaviors than their younger counterparts. Relative to middle-aged female rats once they were sexually experienced, 12 month naïve rats spent less time with the male, were more likely to leave the male after mounts, and displayed fewer solicitation behaviors. Furthermore, 12 month naïve rats failed to discriminate between the stimulus animals, visiting both stimulus animals at the same rate unlike 2 month naïve or 12 month experienced rats. CONCLUSION: Taken together, these results suggest that aging affects some measures of sexual behavior, but most effects of age can be mitigated by regular, repeated mating.

I. Antidepressants and sexual behavior: Weekly ketamine injections increase sexual behavior initially in female and male rats.

The present study characterized the effects of weekly ketamine injections on sexual behavior and anxiety in female and male rats, using a dosing protocol that mimics human therapeutic treatment for depression. In Experiment 1A, ketamine (10 mg/kg, i.p.) or saline was injected once per week for four consecutive weeks. The partner preference paradigm was used to measure sexual motivation 30 min after each weekly injection. Briefly, subjects were first given a 10-min test during which they could choose to spend time in the vicinity of a sexually receptive female stimulus or a sexually experienced male stimulus, however physical contact was restricted (no-contact). Immediately after, subjects were given unrestricted access to the stimulus animals (contact). After a washout period, subjects received four additional weekly injections of ketamine or saline, and then were tested for anxiety-like behavior on the elevated plus maze (EPM) after the last injection (Experiment 1B). For Experiment 2, similar procedures were used to test the effects of weekly ketamine injections on sexual motivation (Experiment 2A) and anxiety (Experiment 2B) in male subjects. In female subjects, ketamine increased sexual motivation as measured by greater time spent with the male stimulus, decreased likelihood of leaving after receiving mounts, and shorter return latencies after receiving intromissions, when compared to saline controls. In male subjects, ketamine shortened latency to first mount and first intromission, as well as increased time spent with the female stimulus. Very little anxiety was observed in either group (ketamine or saline) of female or male subjects when tested on the EPM. In conclusion, even after four weeks of ketamine exposure, sexual dysfunction did not emerge in either females or males. In contrast, ketamine increased sexual motivation in both females and males, with an initial robust response. However, as both groups gained sexual experience, the impact of ketamine diminished.

Zaprinast, a phosphodiesterase type-5 inhibitor, alters paced mating behavior in female rats.

Nitric oxide (NO) is the primary mediator of blood flow in female genital tissues and drugs that enhance the activity of nitric oxide, such as phosphodiesterase type-5 (PDE-5) inhibitors, increase vaginal blood flow in anesthetized rats. The goal of the present study was to test the effects of one PDE-5 inhibitor, zaprinast, on the display of sexual behaviors in gonadectomized, estrogen- and progesterone-treated female rats. Experiment 1 demonstrates that zaprinast alters paced mating behavior by lengthening the contact-return latency to ejaculation; there is a significant relationship between dose of zaprinast (range 1.5-6 mg/kg) and contact-return latency to ejaculation. Experiment 2 illustrates that zaprinast has no effect on preference for an intact male as measured in a No Contact partner preference test. Rats receiving zaprinast tend to exhibit reduced locomotor activity in both experiments. Collectively, these findings demonstrate that modulation of the NO-cGMP pathway using a PDE-5 inhibitor alters the display of paced mating behaviors in rats.

Reproductive success and mate choice in Long-Evans rats.

In the present study, mating behavior was observed in female rats that were given the opportunity to mate with two male rats simultaneously. Eleven sexually naïve, naturally cycling rats were assigned to one pair of sexually experienced cohabitating male rats. Each female rat was mated during proestrous with her assigned pair of males. Eight females successfully became pregnant and gave birth to healthy pups (approximately 9 pups/litter). After the offspring were weaned, paternity of each pup was determined using microsatellite DNA markers. Based on this analysis, it was determined that one male in each pair sired the majority of the pups in the litter. No male sexual behaviors or characteristics distinguished male rats that sired the majority of pups from those that sired few or none of the pups. Furthermore, neither female mate preference nor measures of paced mating behavior differed between male rats that had a reproductive advantage from those that did not. Finally, ejaculation order also failed to predict reproductive success of the male rats. Together, these results suggest that reproductive success of some male rats may not depend on specific mating behaviors, but rather their success may depend on physiological or genetic traits that make them unique.

"What a Girl Wants": What Can We Learn From Animal Models of Female Sexual Motivation?

Sexual motivation is notably different than other motivations such as hunger and thirst, because it lacks homeostatic drive. Sexual motivation poses no threat to physical well-being; individual survival is not at stake. Nevertheless, sexual motivation is a powerful drive and is critical for species survival. Understanding the complexity of sexual motivation has the potential to advance our understanding of other motivations, even pathological motivations, such as those associated with substance abuse. The study of motivation that is unique to females has often been neglected. A number of paradigms have been developed to investigate female sexual motivation beyond measuring only the lordosis reflex. Lordosis is a reflexive posture displayed by female mammals in response to male sexual stimulation to facilitate intromission. The lordosis reflex is essential, but studying the drive to mate is compromised in the absence of robust lordosis. Therefore, appetitive measures of sexual behavior (e.g., preferences, solicitation behaviors) are more specific and more sensitive indicators of sexual motivation than lordosis alone. Paradigms designed to study female sexual motivation often provide a female subject with the choice to interact with a sexually vigorous male or either a non-sexual partner (i.e., female, castrated male) or to remain alone. The study of appetitive measures of sexual motivation has elucidated the role of hormones in female sexual motivation, as well as the underlying neural pathways. The present review describes methods for studying female rats to advance our understanding of sexual motivation and sexual dysfunction.

Intracranial infusions of amphetamine into the medial preoptic area but not the nucleus accumbens affect paced mating behavior in female rats.

The present study evaluated the effects of intracranial administration of amphetamine (AMPH) on paced mating behavior and open field activity in sexually receptive female rats. In Experiment 1, AMPH (0.5 microl of 10 microg/microl) or vehicle was infused bilaterally into the medial preoptic area (mPOA). In Experiments 2 and 3, AMPH (0.5 microl of 40 microg/microl) or vehicle was infused bilaterally into the shell region of the nucleus accumbens (NAc) or core region of the NAc, respectively. In Experiment 1, infusions of AMPH into the mPOA increased the latency to return to the male following sexual stimulation without affecting locomotor activity in the open field test. However, when AMPH was infused 3.0 mm dorsal to the mPOA, no effects were observed. In Experiments 2 and 3, infusions of AMPH into the NAc shell or core significantly increased locomotor activity during the open field test but failed to affect most measures of paced mating behavior. Together these results suggest that amphetamine-stimulate dopamine release in the mPOA but not in the NAc alters paced mating behavior, confirming previous conclusions that the mPOA plays a critical role in female sexual behavior, whereas the NAc plays a relatively limited role.

The effects of ketamine on sexual behavior, anxiety, and locomotion in female rats.

The present study characterized the effects of ketamine on sexual behavior and anxiety in female rats. In Experiment 1, female subjects received an injection of ketamine (10.0mg/kg) or saline 30min prior to a sexual partner-preference test during which each female subject was given the opportunity to interact with a female stimulus or a sexually vigorous male stimulus. Immediately afterwards, female subjects were tested for locomotion in an open field test. Ketamine-treated subjects spent significantly more time with the male stimulus than saline-treated subjects. No other measures of mating behavior (i.e., paced mating behavior, lordosis) were affected by ketamine. Ketamine also had no effect on locomotion. In Experiment 2, female subjects received an injection of ketamine (10.0mg/kg), or saline daily for 10days to investigate the possibility that sexual dysfunction emerges only after repeated exposure. Similar to the results of Experiment 1, ketamine-treated subjects spent significantly more time with the male stimulus than saline-treated subjects. Chronic ketamine treatment also decreased the likelihood of leaving the male after mounts, without affecting any other measures of sexual behavior. Chronic ketamine had no effect on locomotion. In Experiment 3, female subjects received an injection of ketamine (10.0mg/kg) or saline and were tested for anxiety in an elevated plus maze test and for locomotion in an open field test. Acute ketamine had no effect on anxiety or locomotion. In Experiment 4, female subjects received an injection of ketamine (10.0mg/kg) or saline daily for 10days to investigate the possibility that anxiety emerges only after repeated exposure. Chronic ketamine exposure had no effect on any measure of anxiety. However, chronic ketamine exposure increased locomotion. The results from these experiments indicate that unlike other medications prescribed for depression, neither acute nor chronic ketamine treatment causes anxiety or disruption of sexual behavior.

A recreational dose of methylphenidate, but not methamphetamine, decreases anxiety-like behavior in female rats.

Methylphenidate (MPH) and methamphetamine (METH) are two commonly abused psychomotor stimulants that impact anxiety, but in a manner that is currently unclear. This study adds to the literature by testing the effects of MPH and METH on anxiety in adult female rats, which has not previously been studied. In Experiment1, changes in anxiety-like behavior were determined using the Elevated Plus Maze (EPM) following either an acute injection of saline, METH (1 mg/kg), or MPH (10 mg/kg). Changes in general locomotion were measured using the open field test. MPH, but not METH, significantly decreased anxiety; MPH and METH were associated with increased activity in the open field. In Experiment2, we compared the effects of three once daily injections of saline to MPH (10 mg/kg) or METH (1 mg/kg). As with the acute dosing, repeated exposure to MPH, but not METH, decreased anxiety, and both drugs increased locomotion. Neither acute nor chronic dosing produced a change in locomotion during the EPM, indicating that the anxiolytic effects of MPH are independent of changes in locomotor behavior. These findings add further clarification to the literature investigating the psychoactive properties of MPH, with a special and needed emphasis on female behavior.