Time course of VMN lesion effects on lordosis and ultrasound production in hamsters.

Lesions of the ventromedial hypothalamus (VMN) depress lordosis but increase ultrasonic vocalization in female hamsters. These changes are consistent with the behavioral incompatibility of lordosis and ultrasound production and suggest that the VMN coordinates short-term changes in these behaviors. In keeping with past results, unilateral lesions disrupted lordosis responses to contralateral flank stimulation. The change appeared within 15 min after the lesion and was much more rapid than the corresponding effect in rats. For hamsters, these findings support other evidence suggesting VMN mediation of somatosensory, not just hormonal, influences on lordosis. In a companion study, ultrasound rates became depressed within 15 min of bilateral lesion of the VMN, suggesting a role for the VMN in the short-term control of ultrasound production. Calling at later time intervals was facilitated by the lesions. The direction and time course of the lesion effects on lordosis and ultrasound production suggest that the VMN cannot easily account for the behavioral incompatibility of these 2 responses.

Injection of oxytocin into the medial preoptic-anterior hypothalamus increases ultrasound production by female hamsters.

Recent studies of hamsters have documented the facilitation of lordosis and other sociosexual responses by injections of oxytocin (OXT) into the medial preoptic area-anterior hypothalamus (MPOA-AH). These data suggest the regulation of social interaction and bonds by OXT. In turn, this suggests that OXT could act in the MPOA-AH to control other behaviors involved in the initiation or maintenance of social contact, including the ultrasonic vocalizations that female hamsters use to alert and attract potential mates. To test this possibility, we compared the ultrasound rates of 11 naturally estrous hamsters before and after injections of OXT (200 ng/200 nl of saline) or saline (200 nl) into the MPOA-AH. The data revealed a clear facilitation of ultrasound rate 30 min after OXT treatment. This result suggests the modulation of ultrasound rate by endogenous OXT acting within the MPOA-AH. It extends the range of social behaviors sensitive to control by OXT and supports the possibility that OXT acts within the MPOA-AH to facilitate a variety of behaviors involved in the establishment or maintenance of the social interactions required for successful reproduction. At the same time, these data extend earlier observations linking ultrasound production to the MPOA-AH, and begin to describe the peptidergic mechanisms controlling this form of reproductive behavior.

Separation of septal influences on lordosis, ultrasound production, and body weight.

Previous results suggest that septal fibers inhibit lordosis, ultrasound production, and bodily growth (rate of weight gain) in female hamsters. To determine if the systems responsible for these effects can be dissociated, septal connections with or through the preoptic area (POA) were disrupted by horizontal cuts across the interface between these areas. Some subjects received cuts that were centered medially and extended across most of the interface. Others received cuts that were offset laterally and disrupted just the lateral half of this region. Each response was affected by at least one of these cuts. However, the patterns of effects differed across measures. Lordosis was facilitated equally by medial and lateral cuts, suggesting its dependence on fibers that are concentrated where the cuts overlapped, i.e., laterally along the septal-POA interface. In contrast, ultrasound rate was increased just by the more medial cuts, suggesting its dependence on relatively medial fibers. Finally, body weight was increased by both lesions but consistently responded more to the more medial cuts. This suggests that the relevant fibers are distributed across much of the septal-POA interface but are concentrated in its medial half. Taken together, these results suggest that septal connections affecting lordosis, ultrasound production, and body weight follow different trajectories as they enter or leave the ventral septum. In turn, this strengthens the case for the mediation of these effects by distinct populations of septal cells.

Song lateralization in the zebra finch.

The neural mechanisms for bird song commonly are lateralized, depending greatly on the integrity of the left song system and responding much less to manipulations of the system on the right. These results suggest that it is advantageous for the mechanisms controlling song to be lateralized and in this direction. In this context, it is of special interest to study likely exceptions to these rules, for the light they can shed on the functions and mechanisms of song lateralization. Accordingly, we have tested the extent and manner of song lateralization in the zebra finch (Taeniopygia guttata), a species previously identified with an atypical pattern of lateralization. Song by male finches was observed before and after sham operations or transections of the left or right tracheosyringeal nerve. Sham operations failed to affect song. In contrast, males with cuts of the right nerve experienced a depression in fundamental frequency to an apparent baseline of approximately 500 Hz. This effect is consistent with the dominance of the right song system in zebra finches. On the other hand, males with cuts of the left nerve also showed consistent changes, exhibiting frequency increases, especially toward the ends of syllables. The source of these changes is not completely clear. However, rather than challenging the emerging view of lateralization in zebra finches, they may reflect a combination of right dominance and an atypical mechanism for the gating of syringeal airflow and vocalization during song.

Hypothalamic grafts induce the recovery of lordosis in female hamsters with lesions of the ventromedial hypothalamus.

Previous studies have documented the ability of neural grafts to stimulate the recovery of lordosis from neurochemical deficits. However, it was unclear if grafts also could reverse deficits in lordosis caused by lesions at critical points in the neural circuit controlling this response. To address this question, female hamsters were subjected to unilateral lesions of the ventromedial hypothalamus (VMN), a structure well known for its mediation of hormonal effects on lordosis. The effects of these lesions were described by noting the ability of manual stimulation of one flank to reinstate a deteriorating lordosis response. Consistent with past results, unilateral VMN lesions decreased responsiveness to stimulation of just the contralateral flank. Females showing such lateralized decrements then received control treatments or implants into the lesioned area of basal hypothalamic tissue from a neonatal male or female hamster. Approximately 1 month later, tests of lordosis reinstatement by ipsi- or contralateral manual stimuli were repeated. Whereas lateralized decrements in responsiveness persisted in control subjects, implants of tissue from male or female neonates led to reliable improvements in lordosis, reversing the lesion-induced decrease in contralateral responsiveness. The mechanism responsible for this change is unclear, but could involve an elevation in a lordosis-facilitating neuromodulator. Alternatively, it could depend on the reinforcement or replacement of neural circuits for lordosis, possibly including those that connect the two VMNs with each other or with the periaqueductal gray of the midbrain.

Cuts between the septum and preoptic area increase ultrasound production, lordosis, and body weight in female hamsters.

Studies of the mechanisms for female-typical mating behavior have focused on the ventromedial hypothalamus, and on the decrements in lordosis caused by lesions of this structure. However, opposed changes of comparable size are produced, at least in rats, by horizontal cuts extending forward from the anterior commissure (anterior roof deafferentation, or ARD). This suggests the existence of a lordosis-inhibiting system of forebrain structures that may include the lateral septum and preoptic area. To test the generality of this system, ovariectomized hamsters in hormone-induced estrus were observed for levels of ultrasound production and lordosis during tests with male conspecifics. In addition, subjects were observed for lordosis responses to light manual stimulation. Upon the completion of these tests, subjects received control treatments or ARD prior to a second round of behavioral observations. These postoperative tests revealed clear ARD-stimulated increases in ultrasound production and body weight. In contrast, the facilitation of lordosis was more subtle, appearing in tests with manual stimulation, but not in response to males. These results, then, demonstrate some consistency across species in the effects of ARD. At the same time, however, they suggest species differences in the magnitude of these effects, in turn, suggesting species differences in the dependence of receptivity on forebrain lordosis-inhibiting mechanisms.

Dissociation of hypothalamic effects on ultrasound production and copulation.

Two studies were conducted to compare the brain mechanisms for copulation with those controlling other sexual behaviors, such as the ultrasonic calls that help hamsters and other rodents attract potential mates. Specifically, male and female golden hamsters were castrated and hormone-primed prior to being observed for rates of ultrasound production and levels of sex-typical copulatory behavior (mounts, intromissions and ejaculations in males; lordosis in females). Such tests were conducted before and after subjects received sham operations or bilateral lesions of the preoptic area (POA), anterior hypothalamus (AH) or ventromedial hypothalamus (VMN). The results confirmed previous work in showing the POA lesions decrease rates of intromission, ejaculation and ultrasound production, while VMH lesions decrease lordosis duration. More surprising was the tendency of VMN lesions to increase rates of ultrasonic calling by both males and females. For males, these effects identify differences between the neural circuits controlling copulatory and noncopulatory sexual behaviors. For females, they suggest a mechanism for the behavioral incompatibility of ultrasound production and lordosis. In particular, they raise the possibility that the suspension of ultrasonic calling that normally accompanies lordosis reflects an increase in VMN activity that simultaneously provokes lordosis and inhibits vocalization.

Lateralized effects on hamster lordosis of unilateral hormonal and somatosensory stimuli.

To better describe the hypothalamic efferents that mediate estrogenic effects on lordosis, each of 18 ovariectomized hamsters received a 30 gauge implant of estradiol aimed at the right or left ventromedial hypothalamus (VMN). Six days later, subjects were treated with progesterone and observed for their durations of lordosis during brief periods with sexually-active males. Subsequently, the male was removed, as light manual stimulation was applied to the flank ipsi- or contralateral to the implant in attempts to (a) maintain as yet unbroken lordosis responses, or (b) reinstate lordosis in females showing limb movements indicative of their emergence from the male-elicited posture. The results failed to show any difference in the behavioral effects of implants aimed at the right versus left VMN. However, implants did interact selectively with manual stimulation of the ipsi- and contralateral flanks. Specifically, lordosis responses were more likely, more rapid, and better maintained to stimulation of the contralateral flank. This lateralization of the priming effect derived from a VMN estradiol implant is impressive for its persistence, and for its consistency with the trajectories of VMN efferents to the midbrain and of midbrain afferents from the flanks. The consistency of these behavioral and neuroanatomical patterns suggests that lordosis depends on direct interactions of the VMN and dorsal midbrain. In turn, it implicates the dorsal midbrain in the mediation on VMN-initiated hormonal effects on lordosis, and in the eventual integration of hormonal and somatosensory influences on sexual receptivity.

Patterns of 2-deoxyglucose uptake reflect the neural processing of lordosis-inducing somatosensory stimuli in hamsters.

Semi-quantitative [14C]2-deoxyglucose (2DG) autoradiography was used to map the neural responses of female hamsters to lordosis-inducing flank stimuli. Specifically, manual stimulation of one flank was used to maintain estrous females in lordosis for 20 min after an IV injection of 200 muCi/kg of 2DG. Hemispheric differences in 2DG uptake then were sought in brain nuclei implicated in the programming of lordosis, or in the mediation of somatosensory or hormonal influences on this response. The responses to lateralized flank stimulation included reliable contralateral elevations in 2DG uptake in the ventral posterior lateral nucleus of the thalamus (VPL), the dorsal mesencephalic central gray (dCG), and the tectum. Elevated activity on the part of the VPL may not be crucial for lordosis. However, the effects of flank stimulation on 2DG uptake by the dCG and tectum confirm and extend much previous evidence implicating the dorsal midbrain in the mediation of tactile and hormonal effects on sexual responses. For example, these results suggest that somatosensory influences on hamster lordosis are mediated by both the dCG and tectum. In addition, they suggest that these influences are strongly lateralized until at least this stage of sensory processing, leaving for some subsequent element of neural circuitry the task of translating these lateralized inputs into the bilaterally symmetric outputs ultimately required to program the normal, bilaterally symmetric, lordosis response.

Selectivity in the responses of hamsters to conspecific vocalizations.

Lordosis responses by estrous hamsters were triggered by brief manual stimulation. Lordosis durations then were timed, as manual stimulation was discontinued, and subjects were exposed to tape-recordings of conspecific vocalizations reproduced at intensities of 0-60 dB SPL. Relative to the durations observed in the presence of ambient noise alone, recordings of stress-elicited screams failed to facilitate lordosis regardless of stimulus intensity. In contrast, ultrasounds by male or female hamsters did prolong lordosis, and to extents that were directly related to intensity but unrelated to the sex of the caller. The very different responses to screams and ultrasounds suggest that the ability to facilitate sexual behavior is at least somewhat specific to ultrasounds and is not shared by all vocalizations reflecting states of high general arousal. On the other hand, the similar responses elicited by male and female ultrasounds suggest that these calls convey similar messages and that structural differences between them effect changes in call localizability, not meaning.

Localization of hypothalamic sites for the estrogen-priming of sexual receptivity in female hamsters.

Ovariectomized female hamsters received small unilateral implants of estradiol at a variety of anterior-posterior levels of the medial preoptic area and hypothalamus. The results of an initial experiment using 27-ga. implants showed that females with estradiol implants in the ventromedial hypothalamus (VMN) or nearby anterior hypothalamus consistently showed higher levels of sexual receptivity than did females with implants farther rostral, in the preoptic area, or farther caudal, in the posterior hypothalamus. A second experiment used smaller, 28-ga. implants to compare directly the two areas at which implants were effective in the first experiment. The results confirm the findings of other recent studies of hamsters and rats by identifying the VMN as the most effective hypothalamic site for the estrogen priming of sexual receptivity.

Aromatase inhibition depresses ultrasound production and copulation in male hamsters.

Rates of ultrasound production and copulatory behavior were observed in castrated male hamsters maintained on 100 micrograms/day of injected testosterone propionate (TP). Groups matched on their initial levels of behavior received either continued treatment with TP alone, or TP together with 6 mg/day injections of the aromatase inhibitor 1,4,6-androstatriene-3,17-dione (ATD). Testing at 11-15 days after the start of these treatments revealed deficits in the sexual behaviors of the subjects in the latter group. Specifically, these males showed lower rates of ultrasound production and intromission during, as opposed to before, treatment with ATD. These results support previous work suggesting that aromatization plays significant roles in the mediation of androgenic effects on both the courtship and copulatory behaviors of male hamsters.

Hormonal control of sex differences in ultrasound production by hamsters.

Male and female hamsters differ in the stimulus control of the ultrasounds they produce during courtship and mating. In particular, untreated males show greater increases in ultrasound rate after exposure to stimulus females than after contact with other males. Conversely, estrous females are more responsive to stimulus males than females. This sex difference reflects both organizational and activational effects of gonadal hormones. Thus, responses to early castration or treatment with testosterone propionate (TP), estradiol benzoate (EB), or dihydrotestosterone propionate suggest that the development of male-like patterns of ultrasound production is facilitated by perinatal exposure to aromatizable androgen. However, even neonatally feminized subjects will show male-like calling if tested during adult treatment with TP. In contrast, the same subjects respond like naturally estrous females during adult treatment with EB plus progesterone (P). The contrasting responses of neonatally feminized subjects to later TP and EB + P treatments suggest that female hamsters retain a greater capacity for heterotypical patterns of ultrasound production than do males. This obviously differs from the common observation of greater "bipotentiality" for mating behavior in males. In turn, this suggests that the mechanisms controlling sexual bipotentiality are specific to their target behaviors, yielding distinct patterns of hormonal control for at least ultrasound production and lordosis.

Effects of sex and reproductive state on acoustic responsiveness in hamsters.

Semi-quantitative [14C]2-deoxyglucose (2DG) autoradiography was used to describe the responses of hamsters to 35 kHz mimics of the "ultrasounds" used for communication during mating. The first study examined the processing of ultrasounds and ambient noise by estrous females, some of which were deafened or hemideafened with plastic ear plugs. These data failed to reveal responses specific to the ultrasounds. However, lateralized responses to the ambient noise were apparent, especially in the hemideafened subjects. For the ventral cochlear nucleus (VCN), 2DG uptake was elevated contralateral to the plug and ipsilateral to the effective stimulus. In contrast, uptake by more rostral structures (dorsal n. of the lateral lemniscus = DNLL; ventral n. of the lateral lemniscus = VNLL; central n. of the inferior colliculus = CIC; medial geniculate n.) was elevated contralateral to the stimulus. A second experiment examined the responses of intact or castrated male and female hamsters to unilaterally presented ultrasounds and ambient noise. As before, relative levels of 2DG uptake differed across hemispheres for structures including the VCN, trapezoid body, VNLL, DNLL, and CIC. More surprisingly, intact females showed more 2DG uptake than males in the DNLL, auditory nerve, and lateral lemniscus. Females also tended to show elevated anterior hypothalamic uptake, but just in the hemisphere contralateral to the stimulus. These results suggest that male and female hamsters differ in acoustic responsiveness, and that this difference is mediated by hormonal effects at several brainstem components of the central auditory system.

Gold thioglucose-induced brain lesions in hamsters.

Previous studies suggest species differences in the central neural effects of gold thioglucose (GTG). To further assess these differences, we studied the effects of single intraperitoneal injections of GTG on the brains of golden hamsters (Mesocricetus auratus). Within 48 hr of treatment, each of the GTG doses tested (500, 1000 and 1500 mg/kg) had produced lesions in the ventromedial hypothalamus and area postrema. These findings are of interest since they identify the hamster as the first animal known to be susceptible to GTG-induced lesion formation, but resistant to the hyperphagia commonly associated with glucose analog glucoprivation.

Effects of tegmental lesions on lordosis and body weight in female hamsters.

Lordosis responses in naturally-estrous hamsters were elicited by unilateral manual stimulation. Response latencies were compared before and after unilateral lesions of medial and lateral tegmental areas located ventral and ventrolateral, respectively, to the midbrain central gray. The only significant effects were produced by the more lateral lesions. These caused slightly delayed lordosis responses to stimulation of the ipsilateral flank, but had much more pronounced effects on responsiveness to contralateral stimuli, which often entirely failed to elicit lordosis postlesion. This difference in the effectiveness of ipsi- and contralateral stimuli suggests a selective disruption of neural mechanisms involved in the somatosensory control of lordosis initiation. Its locus suggests that a similar mechanism previously identified in the hamster tectum extends ventrally into the dorsal tegmentum, where it overlaps areas implicated in the sensory control of lordosis in other rodents. Since unilateral lesions of the dorsomedial tegmentum failed to affect behavior, a second experiment tested the effects of bilateral medial lesions on male-stimulated lordosis responses in ovariectomized, hormone-primed hamsters. These lesions caused significant increases in body weight, but again failed to show direct effects on lordosis. This result helps to delimit a ventral tegmental system previously implicated in the control of lordosis maintenance in hamsters. In addition, it suggests species differences in the brain circuits involved in the motor control of lordosis.

Facilitation of lordosis by estradiol in the mesencephalic central gray.

Ovariectomized female hamsters received unilateral implants of estradiol aimed at the mesencephalic central gray (MCG). Postoperative levels of lordosis and ultrasonic vocalization were used to evaluate implant effects on sexual receptivity and proceptivity. Females with large MCG implants showed higher levels of receptivity than females with similar implants at control sites. In addition, females with small MCG implants showed little receptivity while the implant served as the sole source of estrogen, but diverged from controls by showing elevated receptivity during supplemental treatment with low systemic doses of estradiol. These results suggest that estradiol implants in the MCG facilitate receptivity if, and only if, accompanied by exposure of other brain areas to low estrogen levels. In turn, this suggests that the MCG, though not a self-sufficient site for the hormonal priming of lordosis, does modulate sexual motivation by mediating facilitatory effects of estrogen on receptivity and mating.

Differential effects of lesions in three limbic areas on ultrasound production and lordosis by female hamsters.

Ultrasound production and lordosis were examined in ovariectomized, hormone-primed female hamsters before and after sham operations or bilateral electrolytic lesions in the lateral septum/bed nucleus, corticomedial amygdala, or lateral habenula. During 2-min exposures to synthetic ultrasounds and 1-min exposures to stimulus males, females with corticomedial amygdala lesions exhibited reduced ultrasound rates and lordosis durations. Following lesions in the lateral septum/bed nucleus, females showed significant increases in ultrasound rates with no pre- to postoperative change in lordosis. Ablations of the lateral habenula had no effect on calling but were associated with shorter lordosis durations. These results demonstrate that two reproductive behaviors, ultrasound production and lordosis, are differentially affected, depending on lesion placement within the limbic system. In turn, these differences demonstrate that the neural mechanisms for two elements of a single major class of behavior can be quite distinct, both in terms of the likelihood that particular brain areas will be involved and in the nature of their involvement.

Delta-9-Tetrahydrocannabinol stimulates receptive and proceptive sexual behaviors in female hamsters.

This experiment studied the effects of delta-9-tetrahydrocannabinol (THC) on lordosis responses and ultrasonic communication (measures of sexual receptivity and proceptivity, respectively) in female hamsters. Specifically, lordosis durations and rates of ultrasound production by estradiol-primed ovariectomized hamsters were observed following acute treatment with 1.5 mg/kg of THC, 500 micrograms of progesterone, or the injection vehicle. The results showed that THC can facilitate both lordosis and ultrasound production. Together with results from other laboratories, these data indicate that THC can stimulate female sexual behavior and suggest that this effect reflects a direct, nonhormonal, effect of THC on brain mechanisms for behavior.