Raúl G. Paredes

What do female rats like about sex? Paced mating.

The motivational aspects of female sexual behavior have been evaluated by a variety of methodologies including: the increasing barrier method, the runway procedure, partner preference test, operant behavior and conditioned place preference. When female rats are tested for sexual receptivity under traditional laboratory conditions, usually a small open area, both appetitive and aversive components of the sexual interaction are easily observed. For example, after prolonged testing, subsequent lordosis and the intensity of this response are reduced increasing the rejection behavior by the female. However, when female rats are allowed to pace (control) the rate of sexual stimulation they received, as usually occurs under seminatural and natural conditions, the aversive properties of mating are reduced. The conditioned place preference can be use to measure the positive affect elicited by mating. We have combined pacing and conditioned place preference in an attempt to reduced the possible aversive consequences associated with mating and increase the likelihood of detecting the appetitive effects of coital interaction in female rats. Only female rats that regulated (paced) their coital interactions with a stud male through a two-compartment chamber in which only the female could freely move from one compartment to the other developed a clear place preference. As well, females that received ten or 15 paced intromissions (without ejaculation) also developed place preference. The place preference induce by paced mating is blocked by the systemic administration of naloxone suggesting that opioids are involved in the reward processes associated with paced mating. Paced sexual interactions can induce a positive affect of sufficient intensity and duration to induce conditioning.

Sexual behavior regulated (paced) by the female induces conditioned place preference.

The possibility that female-paced coital behavior induces a reward state of sufficient intensity and duration to induce conditioning was evaluated by the conditioned-place-preference paradigm. Ovariectomized female rats, treated with estradiol benzoate and progesterone, regulated (paced) their coital interactions with a stud male through a 2-compartment chamber in which only the female could freely move from one compartment to the other. The females that paced their coital interactions showed a clear place preference. In contrast, no change in preference was observed in the females that could not pace their coital contacts. The change in preference in the females that paced their coital interactions was similar to that produced by an injection of morphine (1 mg/kg). These results suggest that coital interactions in females can induce a reward state when the females can control the pace of the sexual interaction.

Only self-paced mating is rewarding in rats of both sexes.

When rats are mated in a traditional mating chamber (with one male and one female) in which the male dictates the pace of the copulatory sequence, males develop a reward state as evaluated by conditioned place preference (CPP). In this mating situation no reward state is induced in females. However, when female rats are able to control (pace) the rate of sexual stimulation, thereby reducing the aversive consequences associated with mating, a clear CPP is observed. In the present study the CPP paradigm was used to determine whether if the reinforced state induced by coital interactions in male rats can be maintained when females pace the sexual interaction. Adult male and female rats were mated in one of two different conditions: (1) where subjects were able to pace their coital interactions or (2) where subjects were not able to pace their sexual contacts. The results showed that when males had control over the sexual interaction they developed a clear place preference while males that mated with females that paced their coital contacts did not develop CPP. Similarly, only females that were able to pace their sexual contacts developed place preference. These results suggest that coital interactions in males, as well as in females, can induce a reward state only when they are able to control the sexual interaction. Under seminatural conditions sexual behavior in rats is highly promiscuous, they mate in groups and repeatedly change partners in the middle of copulation. This behavioral sequence allows both, male and female to control the rate of sexual interaction, assuring the induction of a reward state outlasting the actual performance of coital responses.

Lesions of the medial preoptic area/anterior hypothalamus (MPOA/AH) modify partner preference in male rats

When given the choice, male rats will interact with a receptive female while female rats will interact with a sexually active male. In the present experiment partner preference was tested in male and female rats before and after lesions of the medial preoptic area of the anterior hypothalamus (MPOA/HA). Subjects were gonadectomized, treated for 10 days with 5 microgram/kg of estradiol benzoate (EB) and tested for male coital behavior with receptive females and for partner preference in a three compartment box with free access to either a sexually receptive female or a sexually active male. The same tests were repeated after 10 days of treatment with 5 mg/kg of testosterone propionate (TP). The subjects then received a bilateral electrolytic lesion aimed at the MPOA/AH. Two weeks after the lesion the hormonal treatments and behavioral tests were repeated in the same sequence. Prior to the lesion, females showed a clear preference to interact with the stimulus male while male subjects showed a preference to interact with the receptive female regardless of the hormonal treatment they received. After lesions the females preference for the opposite sex was not modified, they spent more time in the chamber with the stimulus male regardless of whether they had an extensive bilateral destruction of the MPOA/AH or a sham lesion. Males with bilateral destruction of the MPOA/AH changed their partner preference after the lesion. They spent significantly more time in the chamber with the stimulus male than in the chamber with the receptive female. As well, the coital behavior of males with bilateral destruction of the MPOA/AH was significantly reduced after the lesion. The change of preference was observed when the lesioned animals were treated either with EB or TP. The results of the present experiment further support the notion that the MPOA/AH is a crucial structure in the integration of sensory cues that determine partner preference.

Medial preoptic area/anterior hypothalamus and sexual motivation

The medial preoptic area/anterior hypothalamus (MPOA/AH) is a brain site derived from proliferative zones from the diencephalon and telencephalon. It is probably this characteristic that makes this brain region participate in different physiological and behavioral functions. The present review addresses the role of the MPOA/AH in the control of male sexual behavior. It is clear that the MPOA/AH is a crucial site in the control of sexual behavior in males of all species studied to date. But although many different publications have followed the contribution of Heimer and Larsson there is no agreement as to what is specifically the role of the MPOA/AH in sexual behavior. At least three hypotheses have been presented. The first one suggests that this brain region is involved in the consummatory aspects (execution) of sexual behavior. The second indicates that the MPOA/AH is involved in the appetitive components (motivation) of masculine sexual behavior. The third hypothesis considers that MPOA/AH neurons are involved in the regulation of consummatory and appetitive aspects of sexual behavior. From the literature reviewed, it will become evident that the evidence supporting a role of the MPOA/AH in the execution of sexual behavior is based on a number of limited studies not easy to interpret. On the other hand, several lines of evidence using a variety of methodologies support the notion that the MPOA/AH is involved in the motivational aspects of male sexual behavior.

Infusions of naloxone into the medial preoptic area, ventromedial nucleus of the hypothalamus, and amygdala block conditioned place preference induced by paced mating behavior.

Paced mating induces positive affect as revealed by conditioned place preference (CPP) in female rats. It has been suggested that endogenous opioids are involved in the generation of this positive affect since systemic administration of the opioid antagonist naloxone blocks mating-induced CPP. Several brain structures, including the medial preoptic area (mPOA), the ventromedial nucleus of the hypothalamus (VMH), the amygdala (Me), and the nucleus accumbens (Acb) have been implicated in the control of female sexual behavior. However, it is not known if these structures also participate in the positive affect produced by paced mating. To this end we determined the effects of intracranial administration of naloxone methiodide into the mPOA, VMH, Me and Acb on conditioned place preference induced by paced mating in female rats. Regardless of the site of infusion 5 micro of naloxone did not affect any of the sexual behavior parameters measured during copulation. When CPP was evaluated, the groups infused with naloxone into the mPOA, the VMH, and the Me before each conditioning session did not develop place preference. Only the group infused with naloxone in the Acb and the control groups did so. These results demonstrate that opioid receptors within the mPOA, VMH and Me are necessary for the rewarding aspects of paced mating. We suggest that the Me and VMH are important for the transmission of sensory information produced by copulation while the mPOA is the site where the positive affect is originated.

Effect of prenatal androgen receptor antagonist or aromatase inhibitor on sexual behavior, partner preference and neuronal Fos responses to estrous female odors in the rat accessory olfactory system

Many socially relevant odors are detected in rodent species by the vomeronasal organ and subsequently processed by the accessory olfactory system (AOS). We previously found that gonadectomized male and female rats treated in adulthood with testosterone propionate (TP) showed equivalent Fos responses in the AOS to odors derived from estrous females. Likewise, in contrast with numerous other mammalian species, gonadectomized female rats show surprisingly high levels of male-typical mounting behavior in response to adult TP. We tested the hypothesis that prenatal testosterone (T) exposure, acting via androgen receptors (ARs) or via estrogen receptors, masculinizes the AOS in rats of both sexes. Pregnant dams were treated with either the AR blocker, Flutamide, the aromatase inhibitor, 1,4,6-androstatriene-3,17-dione (ATD), or nothing (control) to assess the role of prenatal androgen and estradiol receptor activation, respectively, in this masculinization. Beginning at birth, male and female offspring were injected subcutaneously (sc) every other day with either ATD (pre- and neonatal ATD group) or oil vehicle (Flutamide and control groups) until postnatal Day 12. Subjects were gonadectomized as adults, hormonally treated and tested for different behaviors before having their AOS Fos responses to estrous female odors assessed. Prenatal treatment with Flutamide (but not ATD) significantly decreased anogenital distance and severely impaired intromissive and ejaculatory behaviors in males tested after TP replacement without disrupting mounting capacity in either sex. Pre- and neonatal treatment with ATD (but not Flutamide) enhanced lordosis responsiveness in males tested after sc injections of estradiol and progesterone, whereas these perinatal treatments had no effect on any aspect of masculine coital performance in either sex. After TP treatment, male and female control subjects preferred to approach a tethered stimulus female as opposed to a male, and prenatal Flutamide or perinatal ATD treatments did not modify this pattern of partner preference. Neuronal Fos responses to estrous odors were (as in previous studies) identical in the AOS of gonadectomized TP-treated control males and females. Prenatal Flutamide or perinatal ATD treatments failed to disrupt consistently this profile of Fos responses to estrous odors in the AOS of rats of either sex. These behavioral and neuroanatomical findings raise the possibility that the similar level of male-typical responsiveness to social odors that occurs in male and female rats after adult TP treatment results from nonsteroid-hormone-dependent, species-specific factors that act perinatally in the brains of rats of both sexes.

Dopamine antagonists do not block conditioned place preference induced by paced mating behavior in female rats.

The authors assessed the behavioral effects of dopamine (DA) receptor antagonists, Cis (Z) flupentixol and S(+)-raclopride L-tartrate, on conditioned place preference (CPP) induced by paced mating behavior. Ovariectomized female rats of the Wistar strain were used. The administration of amphetamine (1 mg/kg) induced a clear CPP that was completely blocked by the DA antagonists flupentixol (0.25 mg/kg) or raclopride (0.125 mg/kg). These doses had no effect on motor coordination. Female rats that mated in a pacing chamber developed a clear CPP. Neither flupentixol nor raclopride blocked the reward state induced by paced mating behavior. These results indicate that DA is not involved in the reward state induced by paced mating behavior in female rats.

Comparative analysis of immunoreactive cells for androgen receptors and oestrogen receptor alpha in copulating and non-copulating male rats.

In some species, including gerbils, guinea pigs, mice, rams and rats, some apparently normal males fail to mate. These kinds of animals have been named ‘noncopulating (NC)’. The cause of this behavioural deficit is unknown. The present study aimed to determine whether NC male rats have alterations in the amount of androgen (AR) and oestrogen receptor α (ERα) in a neuronal circuit important for the control of male sexual behaviour; the vomeronasal projection pathway. We evaluated the number of AR and ERα immunoreactive (AR‐IR and ERα‐IR) cells in the accessory olfactory bulb (AOB), the bed nucleus of the stria terminalis (BNST), the anterior‐dorsal medial amygdala (MeAD), the posterior dorsal amygdala (MePD) and the medial preoptic area (MPOA). The results demonstrate that the number of AR‐IR cells in NC males was significantly higher compared to copulating (C) males in the MePD, but no significant differences were found in any of the other structures analysed. ERα‐IR cells were more abundant in NC than in C males in the MeAD and the MePD. However, in the MPOA the number of ERα‐IR cells was significantly reduced in NC males. No significant differences were found in the AOB or in the BNST. A similar pattern of results was observed when regions within these structures that are activated by Fos expression, on mating or exposure to sexually relevant cues were analysed. The differences in the number of AR and ER in particular brain areas could be associated with alterations in sexual behaviour as well as partner and olfactory preference for receptive females seen in NC male rats.

Inactivation of the medial preoptic area/anterior hypothalamus by lidocaine reduces male sexual behavior and sexual incentive motivation in male rats.

Permanent bilateral lesions of the medial preoptic area anterior hypothalamus (MPOA/AH) produce a drastic inhibition of male sexual behavior in all species studied to date. The present experiment was designed to evaluate if temporal inactivation of the MPOA/AH by infusions of lidocaine also inhibits sexual behavior in male rats. This would allow us to rule out the possibility that the behavioral effects observed after damage of the MPOA/AH could be associated with plastic changes induced by the lesion in other brain regions. We also evaluated sexual incentive motivation in males after the infusion of lidocaine in a test in which copulation is not possible but where males maintain approach behavior to the estrous females despite repeated testing. The percentage of animals displaying mounts, intromissions and ejaculation was significantly reduced while mount and intromission latency were prolonged after infusion of lidocaine. No changes were observed in sexual behavior after infusion of lidocaine in animals with cannulae outside the MPOA/AH suggesting that the inhibitory effects are specific to this brain region. Sexual incentive motivation was also affected by administration of lidocaine. Males consistently showed a clear preference for the sexually receptive female except when infused with lidocaine. After the infusion of the compound a significant reduction in the time spent in the incentive zone of the stimulus female was observed. These results support the hypothesis that neurons of the MPOA/AH are involved in the control of male sexual motivation.