"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.

Exposure to methylphenidate during peri-adolescence affects endocrine functioning and sexual behavior in female Long-Evans rats.

The present study was designed to test the effects of methylphenidate (MPH) exposure on the maturation of endocrine functioning and sexual behavior. Female rat pups received either MPH (2.0mg/kg, i.p.) or saline twice daily between postnatal days 20-35. This period of exposure represents the time just prior to puberty as well as puberty onset. Approximately five weeks after the last injection of MPH or saline, female subjects were hormone-primed and tested during their first sexual experience. Subjects were given the choice to interact with a sexually active male or a sexually receptive female rat (i.e., the partner-preference test). The partner-preference paradigm allows us to assess multiple aspects of female sexual behavior. MPH exposure during peri-adolescence delayed puberty and, when mated for the first time, affected sexual behavior (e.g., increased time spent with the male stimulus and decreased the likelihood of leaving after mounts) during the test of partner preference. When monitoring estrous cyclicity, female subjects treated with MPH during peri-adolescence frequently experienced irregular estrous cycles. The results of the present study suggest that chronic exposure to a therapeutic dose of MPH around the onset of puberty alters long-term endocrine functioning, but with hormone priming, increases sensitivity to sexual stimuli.

Acute withdrawal but not long-term withdrawal from methamphetamine affects sexual behavior in female rats.

The present study was designed to investigate the long-term effects of repeated methamphetamine (MA) exposure on sexual motivation in female rats tested after a period of drug abstinence. In Experiment 1, female subjects received three injections of MA (1.0mg/kg/day, every other day) or saline and were tested for paced mating behavior (where females could control the receipt of sexual stimulation from one male rat) 21 days after their last injection. In Experiment 2, female subjects received 12 consecutive injections of MA (1.0mg/kg/day) or saline and were tested for mate choice (where females could control the receipt of sexual stimulation from two male rats simultaneously) 6 days after their last injection. Experiment 3 was identical to Experiment 2 except that female subjects received no baseline mating test and were tested for mate choice 24h and 6 days after their last injection. Open field tests were conducted in each experiment to measure locomotor activity after repeated exposure to MA. Although repeated MA exposure increased locomotor activity, mating behavior was not facilitated after either a short (6 days) or long (21 days) period of drug abstinence. Nevertheless, sexual behavior was disrupted during the 24h acute withdrawal period. Therefore, although the present study found no evidence of cross-sensitization between female sexual behavior and MA after either a short or a long period of drug abstinence, sexual behavior in sexually naïve female rats is sensitive to the depressive state associated with acute withdrawal from MA. In conclusion, the results of the present study suggest that MA acts differently from other psychomotor stimulants, and that the effects of MA withdrawal on sexual behavior differ between male and female rats.

Updating of the spatial reference frame of head direction cells in response to locomotion in the vertical plane.

Many species navigate in three dimensions and are required to maintain accurate orientation while moving in an Earth vertical plane. Here we explored how head direction (HD) cells in the rat anterodorsal thalamus responded when rats locomoted along a 360° spiral track that was positioned vertically within the room at the N, S, E, or W location. Animals were introduced into the vertical plane either through passive placement (experiment 1) or by allowing them to run up a 45° ramp from the floor to the vertically positioned platform (experiment 2). In both experiments HD cells maintained direction-specific firing in the vertical plane with firing properties that were indistinguishable from those recorded in the horizontal plane. Interestingly, however, the cells' preferred directions were linked to different aspects of the animal's environment and depended on how the animal transitioned into the vertical plane. When animals were passively placed onto the vertical surface, the cells switched from using the room (global cues) as a reference frame to using the vertically positioned platform (local cues) as a reference frame, independent of where the platform was located. In contrast, when animals self-locomoted into the vertical plane, the cells' preferred directions remained anchored to the three-dimensional room coordinates and their activity could be accounted for by a simple 90° rotation of the floor's horizontal coordinate system to the vertical plane. These findings highlight the important role that active movement signals play for maintaining and updating spatial orientation when moving in three dimensions.

Methamphetamine enhances sexual behavior in female rats.

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 (1.0mg/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 (1.0mg/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.

Contextual control of inhibition with reinforcement: adaptation and timing mechanisms.

Four experiments with rats studied the effects of switching the context after Pavlovian conditioning. In three conditioned suppression experiments, a large number of conditioning trials created "inhibition with reinforcement" (IWR), in which fear of the conditional stimulus (CS) reached a maximum and then declined despite continued CS-unconditional stimulus pairings. When IWR occurred, a context switch augmented fear of the CS; IWR and augmentation were highly correlated. Neither IWR nor augmentation resulted from inhibition of delay (IOD): In conditioned suppression, IWR and augmentation occurred without IOD (Experiment 3), and in appetitive conditioning (Experiment 4), IOD occurred without IWR or augmentation. IWR may occur in conditioned suppression because the animal adapts to fear of the CS in a context-specific manner. The authors discuss several implications.

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.

Path integration and lesions within the head direction cell circuit: comparison between the roles of the anterodorsal thalamus and dorsal tegmental nucleus.

Experiments were designed to determine whether 2 regions of the head direction cell circuit, the anterodorsal thalamic nucleus (ADN) and the dorsal tegmental nucleus (DTN), contribute to navigation. Rats were trained to perform a food-carrying task with and without blindfolds prior to receiving sham lesions or bilateral lesions of the ADN or DTN. ADN-lesioned rats were mildly impaired in both versions of the task. DTN-lesioned rats, however, were severely impaired and showed reduced heading accuracy in both task versions. These findings suggest that although both the DTN and ADN contribute to navigation based on path integration and landmarks, disruption of the head direction cell circuit at the level of the DTN has a significantly greater effect on spatial behavior than lesions of the ADN.