Processes regulating the initiation and postejaculatory resumption of copulatory behavior in male hamsters.

Studies using factor analysis have helped describe the organization of copulatory behavior in male rodents. However, the focus of these studies on a few traditional measures may have limited their results. To test this possibility, 74 sexually-experienced male hamsters were observed as they copulated with stimulus females. The measures collected exceeded the conventional ones in number, variety and independence. The factor analysis of these data revealed a structure with seven factors collectively accounting for 80% of the variance. Most resembled the factors in previous reports, reinforcing the contributions that the processes suggested by these factors make to the organization of male behavior. But several other factors were more novel, possibly reflecting the use of measures that were novel or revised for greater independence. The most interesting of these were two factors focusing on early steps in the progression leading to ejaculation. Importantly, both incorporated measures from each of the three copulatory series that were observed. Past work suggests that independent processes control the times required to initiate copulation and later resume it after an ejaculation. In contrast, these results suggest the existence of two processes, each of which contributes to both the initiation and reinitiation of copulation.

Role of acetylcholine in control of sexual behavior of male and female mammals.

The results of studies using systemic or central applications of cholinergic drugs suggest that acetylcholine makes important contributions to the neurochemical control of male- and female-typical reproductive behaviors. In males, cholinergic control seems largely specific to some elements or aspects of copulatory behavior that can vary significantly across species. Synapses in or near the medial preoptic area represent part of this mechanism, but the entire system appears to extend more widely, perhaps especially to one or more structures flanking some part of the lateral ventricle. In females, the lordosis response that essentially defines sexual receptivity is clearly responsive to cholinergic drugs. The same seems likely to be true of other elements of female sexual behavior, but additional studies will be needed to confirm this. Changes in cholinergic activity may help to mediate estrogenic effects on female sexual behavior. However, estrogen exposure can increase or decrease cholinergic effects, suggesting a relationship that is complex and requires further analysis. Also presently unclear is the localization of the cholinergic effects on female sexual responses. Though periventricular sites again have been implicated, their identity is presently unknown. This review discusses these and other aspects of the central cholinergic systems affecting male and female sexual behaviors.

Rapid facilitation of ultrasound production and lordosis in female hamsters by horizontal cuts between the septum and preoptic area.

Horizontal cuts between the septum and preoptic area (anterior roof deafferentation, or ARD) dramatically affect sexual behavior, and in ways that could explain a variety of differences across behavioral categories (precopulatory, copulatory), species, and the sexes. Yet little is known about how these effects develop. Such information would be useful generally and could be pivotal in clarifying the mechanism for ultrasonic vocalization in female hamsters. Ultrasounds serve these animals as precopulatory signals that can attract males and help initiate mating. Their rates can be increased by either ARD or lesions of the ventromedial hypothalamus (VMN). If these effects are independent, they would require a mechanism that includes multiple structures and pathways within the forebrain and hypothalamus. However, it currently is not clear if they are independent: VMN lesions could affect vocalization by causing incidental damage to the same fibers targeted by ARD. Fortunately, past studies of VMN lesions have described a response with a very distinctive time course. This raises the possibility of assessing the independence of the two lesion effects by describing just the development of the response to ARD. To accomplish this, female hamsters were observed for levels of ultrasound production and lordosis before and after control surgery or ARD. As expected, both behaviors were facilitated by these cuts. Further, these effects began to appear by two days after surgery and were fully developed by six days. These results extend previous descriptions of the ARD effect by describing its development and time course. In turn, the rapid responses to ARD suggest that these cuts trigger disinhibitory changes in pathways that differ from those affected by VMN lesions.

Oxotremorine delays and scopolamine accelerates sexual exhaustion when applied to the preoptic area in male hamsters.

Acetylcholine (ACh) has not been tested for a role in the development of sexual exhaustion in males. However, male hamsters receiving infusions into the medial preoptic area (MPOA) of the muscarinic agonist oxotremorine (OXO) or antagonist scopolamine (SCO) show changes in the postejaculatory interval, one of the measures that changes most consistently as exhaustion approaches. In addition, central SCO treatments cause changes in the patterning of intromissions that resemble those signaling exhaustion. To extend these observations and more thoroughly test the dependence of sexual exhaustion on ACh, male hamsters received MPOA treatments of OXO, SCO or the combination of the two before mating to exhaustion. Relative to placebo, OXO infusions caused small but consistent increases in ejaculation frequency and long intromission latency, delaying the appearance of exhaustion. Scopolamine treatments did the reverse, dramatically accelerating the development of exhaustion. Consistent with and possibly responsible for these changes were effects on the quality of performance prior to exhaustion. These included differences in overall copulatory efficiency (e.g., ejaculations/intromission), which was increased by OXO and decreased by SCO. They also extended to several standard measures of copulatory behavior, including intromission frequency, ejaculation latency and the postejaculatory interval: Most of these were increased by SCO and decreased by OXO. Finally, whereas most or all effects of OXO were counteracted by SCO, most or all of the responses to SCO resisted change by added OXO. This asymmetry in the responses to combined treatment raises the possibility that the effects of these drugs on sexual exhaustion and other elements of male behavior are mediated by distinct muscarinic receptors.

Responses to central oxotremorine and scopolamine support the cholinergic control of male mating behavior in hamsters.

The responses of hamsters to intracranial injections of the cholinergic agonist oxotremorine (OXO) implicate cholinergic mechanisms in the medial preoptic area (MPOA) in the control of male mating behavior. To extend these observations, we ran three studies of responses to cholinergic drugs delivered singly or in combination to the vicinity of the MPOA. The first tested responses to OXO, confirming its ability to reduce the postejaculatory interval. The second complemented the first by examining responses to MPOA microinjections of the cholinergic antagonist scopolamine (SCO). These caused several changes revolving around intromission. These included increases in intromission frequency and ejaculation latency. They also included a change in the patterning of intromissions, marked by continuous strings without the usual separation by dismounts. The final study resembled the others in examining the effects of MPOA injections of OXO and SCO but focused on the ability of each drug to antagonize responses to the other. Most of the responses to OXO and SCO individually replicated earlier findings, though the measures examined here also permitted the description of effects on some noncopulatory sexual behaviors, specifically the male's inspection of the female. However, the most interesting results may be those suggesting asymmetry in the responses to the addition of the second drug: Whereas responses to OXO tended to be antagonized by SCO, OXO was less effective at counteracting responses to SCO. Though the explanation of this asymmetry is not completely clear, it is consistent with previous suggestions of differences in the affinities of these drugs for subtypes of muscarinic receptors. Therefore, it suggests that the cholinergic synapses and circuits controlling distinct elements of male behavior could differ in their dependence on these receptors.

Effects of apomorphine on mating behavior, flank marking and aggression in male hamsters.

In male rats, the dopamine agonist apomorphine (APO) generally facilitates copulatory behavior. However, disruptive effects of high APO doses have been reported. These have been interpreted in diverse ways, as products of a dopaminergic system that inhibits sexual behavior or as consequences of APO's stimulation of competing responses. To test the generality of these effects, we observed APO's impact on copulatory behavior in male hamsters. Several effects were observed, all attributable to a relatively high dose and involving the disruption of male behavior. More unexpectedly, APO treatment caused males to attack estrous stimulus females in the course of these tests. To clarify these effects, we observed the effects of APO on flank marking, a type of scent marking closely allied to aggression and dominance in hamsters. Treatment reliably decreased the latency of marking. It also increased the rate of marking when appropriate measures were taken to prevent this effect from being obscured by drug-induced cheek pouching. Together, these results confirm and extend APO's well-known ability to increase aggression. Further, they suggest that APO-induced aggression can intrude into other contexts so as to disrupt, or possibly facilitate, other forms of social behavior.

Cholinergic control of male mating behavior in hamsters: effects of central oxotremorine treatment.

The responses of rats to intracranial injections of cholinergic drugs implicate acetylcholine in the control of male mating behavior and suggest specific brain areas as mediators of these effects. In particular, past work has linked the medial preoptic area (MPOA) to the control of intromission frequency but implicated areas near the lateral ventricles in effects on the initiation and spacing of intromissions. Studies of responses to systemic cholinergic treatments suggest that acetylcholine is even more important for the control of mating behavior in male hamsters but provide no information on the relevant brain areas. To fill this gap, we observed the effects of central injections of the cholinergic agonist oxotremorine that approached the MPOA along contrasting paths. Both studies suggest that increased cholinergic activity in or near the MPOA can facilitate behavior by reducing the postejaculatory interval and possibly affecting other parts of the mechanisms controlling the initiation of copulation and the efficiency of performance early in an encounter. In addition, oxotremorine caused other changes in behavior that could not be tied to the MPOA and may reflect actions at more dorsal sites, possibly including the bed nucleus of the stria terminalis and medial septum. These effects were notably heterogeneous, including facilitatory and disruptive effects on male behavior along with a facilitation of lordosis responses to manual stimulation. These results emphasize the number and diversity of elements of sexual behavior in hamsters that are under the partial control of forebrain cholinergic mechanisms.

Cholinergic control of male mating behavior in hamsters: effects of systemic agonist or antagonist treatment.

Sexual behavior in male rats is thought to depend in part on central cholinergic activity. In particular, previous studies of responses to systemically administered cholinergic drugs suggest that male rat behavior can be facilitated by the muscarinic agonist oxotremorine but is disrupted by the muscarinic antagonist scopolamine. However, it is not clear how broadly these effects generalize across species. To address this issue, we observed the impact on sexual behavior in male hamsters of systemic treatment with oxotremorine or scopolamine. In each case, the peripheral muscarinic antagonist methylscopolamine was used as an auxiliary or control treatment to better isolate central cholinergic effects. Both oxotremorine and scopolamine disrupted male behavior in hamsters. For example, both increased the likelihood of failure to achieve intromission or ejaculation. Further, even on completed tests oxotremorine treatment led to changes including increases in mount latency and postejaculatory interval while scopolamine treatment caused changes including increases in ejaculation latency and intromission frequency. The many changes caused by these treatments suggest that acetylcholine helps to control many elements of male behavior, probably by acting at multiple brain sites. The generally similar responses to a cholinergic agonist and antagonist suggest the dependence of efficient mating behavior on optimal levels of central cholinergic activity.

Organization of mating behavior in male hamsters (Mesocricetus auratus).

Factor analysis was applied to standard measures of sexual behavior in 73 male hamsters (Mesocricetus auratus) as they interacted with hormone-primed females. The results suggest that 5 factors, or conceptual mechanisms, function in the organization of the behaviors observed in the first 2 copulatory series. Of these, the 3 that relate to the behaviors in the first copulatory series were compared to those emerging from prior analyses of other rodents. These comparisons revealed similarities and differences in factor structure across species. Whereas all of these analyses identify factors related to the initiation and efficiency of copulatory behavior, hamsters seem to differ from other species in the measures that best define these factors. In addition, the copulatory rate factor that has been prominent in previous analyses of rats seems to be absent in hamsters. These results suggest that male sexual behavior in hamsters is organized differently from that in other rodents. In more general terms, they suggest that even species with generally similar copulatory patterns can show significant differences in behavioral organization, in turn suggesting the need for additional factor analytic studies to better establish the extent of these species differences.

Effects of damage to auditory cortex on the discrimination of speech sounds by rats.

The intensity of a noise-induced startle response can be reduced by the presentation of an otherwise neutral stimulus immediately before the noise ("prepulse inhibition" or PPI). We used a form of PPI to study the effects of damage to auditory cortex on the discrimination of speech sounds by rats. Subjects underwent control surgery or treatment of the auditory cortex with the vasoconstrictor endothelin-1. This treatment caused damage concentrated in primary auditory cortex (A1). Both before and after lesions, subjects were tested on 5 tasks, most presenting a pair of human speech sounds (consonant-vowel syllables) so that the capacity for discrimination would be evident in the extent of PPI. Group comparisons failed to reveal any consistent lesion effect. At the same time, the analysis of individual differences in performance by multiple regression suggests that some of the temporal processing required to discriminate speech sounds is concentrated anteroventrally in the right A1. These results also confirm that PPI can be adapted to studies of the brain mechanisms involved in the processing of speech and other complex sounds.

Effects on hamster vocalization and aggression of carbachol injections into the MPOA/AH.

Recent work has shown that microinjections of the cholinergic agonist carbachol into the preoptic area (MPOA) increase 20-30 kHz ultrasonic vocalization in rats. This response could be interpreted as a quite specific and direct effect on a central mechanism for vocalization or ultrasound production. Alternatively, it could reflect a more general drug-induced increase in defensiveness or defensive aggression. Two studies were conducted to distinguish these possibilities. In both, MPOA carbachol treatments very similar to those in previous work (unilateral injections into the MPOA/AH of 1 microg of carbachol in 0.2 microl of saline) were administered to female hamsters. The first study focused on the rate of ultrasonic courtship vocalization, finding it to decrease after treatment. This result is inconsistent with the view that cholinergic agonists directly stimulate vocalization. In contrast, although it does not completely exclude an effect on a mechanism for vocalization, it provides at least suggestive support for an interpretation in terms of defensiveness: Because hamster ultrasounds convey sexual readiness rather than alarm or aggressiveness, they would be expected to decrease in the event of a drug-induced increase in an incompatible motivational or emotional state. The second study exploited the aggressiveness of hamsters to even more directly test carbachol's ability to increase defensiveness or defensive aggression. Its results showed that minimally-estrous female subjects bit their male pursuers more quickly if recently treated with carbachol rather than placebo. Taken together, both results support the existence of a cholinergic system that extends through the MPOA and regulates defensiveness or a related motivational or emotional state.

Differential reductions in acoustic startle document the discrimination of speech sounds in rats.

The intensity of a noise-induced startle response can be reduced by the presentation of an otherwise neutral stimulus immediately before the noise ("prepulse inhibition" or PPI). This effect has been used to study the detection of gaps and other stimuli, but has been applied infrequently to complex stimuli or the ability to discriminate among multiple stimuli. To address both issues and explore the potential of PPI, rats were presented a series of 5 tasks, most contrasting a pair of speech sounds. One of these (the "standard" stimulus) occurred frequently but rarely preceded the startle stimulus. The second occurred infrequently (as an "oddball") and always preceded a noise. In each such task, startle responses were inhibited more by the oddball than by the standard stimulus, usually within the first test. This suggests that PPI can be adapted to studies of the discrimination of speech and other complex sounds, and that this method can provide useful information on subjects' ability to discriminate with greater ease and speed than other methods.

Effects of midbrain lesions on lordosis and ultrasound production.

Previous studies suggest the control of lordosis by competing neural systems. A lordosis-inhibiting system is thought to originate in the lateral septum (LS) or preoptic area (POA) and project to midbrain sites, including the ventral tegmental area (VTA) and ventral half of the periaqueductal gray (vPAG). A lordosis-facilitating system is thought to originate in the ventromedial hypothalamus and project to the dorsal half of the PAG (dPAG). To test the generality of this model, we subjected female hamsters to control operations or lesions of the dPAG, vPAG or VTA. Subjects in hormone-induced estrus were observed for lordosis responses to males and manual stimulation and for rates of production of the "ultrasounds" used by hamsters for courtship. PAG lesions of both types depressed ultrasound rate, lordosis initiation and lordosis maintenance. VTA lesions failed to affect ultrasound rate, lordosis maintenance or lordosis responses to males. However, damage to the dorsomedial tegmentum was correlated with deficits in lordosis initiation. These results suggest the concentration in the PAG of mechanisms controlling vocalizations, including the ultrasounds used by hamsters for courtship. They confirm midbrain control of lordosis initiation and maintenance but fail to support any simple specialization of dorsal and ventral areas for these dimensions. They also fail to support a specialization of the dorsal and ventral halves of the midbrain for lordosis facilitation and inhibition, but do suggest several midbrain areas likely to be involved in the first of these functions.

Time course of VMN lesion effects on lordosis and proceptive behavior in female hamsters.

Previous studies suggest that ultrasound production by female hamsters is better able than other reproductive behaviors to recover from an initial drop caused by damage to the ventromedial hypothalamus (VMN). At the same time, few studies have examined the time course of such lesion effects. To remedy this, female hamsters were observed before and after control operations or VMN lesions. The behaviors considered were ultrasound production, lordosis, approach, and vaginal marking. Ultrasound production, lordosis, and approach were affected by lesions, permitting the description of the time course of each of these effects. Only ultrasound rates showed evidence of recovery, which culminated in rates significantly above those observed preoperatively in the same animals. This suggests that ultrasound production is unusual in its response to VMN damage and that the underlying mechanism could be of interest in studies of the processes that determine recovery from brain damage.