Inhibition Of Sexual Behavior Research Articles

Different receptor mechanisms mediate the effects of endotoxin and interleukin-1 on female sexual behavior

Activation of the immune system by lipopolysaccharide (LPS) produces physiological, neuroendocrine and behavioral effects, some of which are mediated by cytokine production. We have previously shown that the cytokine interleukin-1 (IL-1) inhibits sexual behavior in female, but not male rats, while producing a comparable suppression of locomotion in both sexes. The present study examined the effects of LPS on sexual behavior and locomotion of male and female rats, and the involvement of IL-1 receptors in mediating the effects of IL-1 and LPS on females' behavior. Peripheral (i.p.) administration of LPS (50 or 250 μg/kg) significantly decreased sexual behavior in females, up to 6 h after administration, while it had no effect on male sexual behavior. However, locomotor activity, measured in the open-field test, was similarly reduced by LPS in both males and females. Pretreatment with the IL-1 receptor antagonist (IL-1ra) either i.p. (10 mg/kg) or intracerebroventricularly (i.c.v.) (50 μg/rat) did not prevent the inhibition of female sexual behavior and locomotion induced by either i.p. (50 μg/kg) or i.c.v. (200 or 400 ng/rat) administration of LPS, respectively. However, identical doses of IL-1ra significantly reversed the effects of IL-1β, administered either i.p. (5 μg/kg) or i.c.v. (50 ng/rat), respectively. These results demonstrate that both LPS and IL-1β produce marked inhibition of sexual behavior in female, but not in male rats. However, IL-1 receptors are not required for the effects of LPS on sexual behavior in female rats.

GABAergic Drugs and Socio-Sexual Behavior

To elucidate the role of GABA in the control of sexual behavior, the effects of the GABA A agonist 4,5,6,7-tetrahydroisoxazolo[5,4 c]-pyridin-3-ol (THIP), the GABA transaminase inhibitors sodium valproate and γ-acetylen-GABA (GAG), and the GABA synthesis inhibitors isoniazide and deoxypyridoxine were evaluated in sexual behavior, exploration, and sociosexual interactions with a receptive female or a castrated male. Furthermore, to discriminate possible general inhibitory effects from those specific to sexual behavior, the doses of the drugs that produced a significant inhibition of copulation were tested in a free drinking procedure. THIP (16 mg/kg), sodium valproate (400 mg/kg), GAG (100 mg/kg), and deoxypyridoxine (400 mg/kg) produced a strong inhibition of sexual behavior. The percentage of animals displaying mounts and intromissions as well as the mean number of mounts and intromissions were significantly reduced. Sociosexual interactions with a receptive female or a castrated male and exploratory behaviors were also reduced. The most consistent effects observed were reductions in sniffing, self-grooming, and rearing. Drinking behavior was significantly reduced in doses that inhibited sexual behavior. These results further support the hypothesis that altered GABAergic neurotransmission produces reduced sensitivity to environmental stimuli and thereby inhibits sexual and drinking behavior in a nonspecific way.

Behavioral and social correlates of escape from suppression of ovulation in female common marmosets housed with the natal family.

Although female common marmosets typically do not breed while housed with their natal families, up to half ovulate at least once while housed with the intact natal family, and a similar proportion conceive if an unrelated adult male is present in the group. In this study, we investigated the behavioral and social correlates of escape from suppression of ovulation by daughters housed in intact natal families or in families in which the father had been replaced by an unrelated adult male. Focal-animal behavioral data were collected from daughters that were (N = 7) or were not (N = 10) undergoing ovulatory cycles while housed with the natal family and from daughters that were (N = 5) or were not (N = 3) cycling or pregnant in families containing an unrelated male. Additionally, four cyclic and six acyclic females housed in intact natal families underwent simulated "prospecting" tests. Cyclic and acyclic daughters in intact natal families did not engage in sexual interactions with the father and showed few differences from one another in their interactions with the parents. Moreover, cyclic and acyclic daughters did not differ in their willingness to leave the family for short periods or to investigate an unfamiliar family in "prospecting" tests. However, daughters that underwent ovarian cycles in the presence of an unrelated male showed numerous behavioral differences from those in intact natal families, including frequent courtship and sexual behaviors with the male, reduced affiliative interactions with the mother, and elevated frequencies of aggressive display behavior. Moreover, these females were less likely to behave submissively towards the mother or the adult male. These findings suggest that both suppression of ovulation and inhibition of sexual behavior normally contribute to reproductive failure in female marmosets living with their natal families, and that the two components of suppression may become dissociated under specific social conditions.

Inhibition of sexual behaviour and the luteinizing hormone surge by intracerebral progesterone implants in the female sheep

In female sheep, progesterone blocks the induction by oestradiol of both sexual behaviour and the pre-ovulatory surges of gonadotrophin releasing hormone (GnRH) and luteinising hormone (LH). However, the central sites of action of progesterone remain poorly defined, so we attempted to locate them by implanting progesterone intracerebrally in ovariectomised ewes treated with exogenous steroids to induce oestrous behaviour and the LH surge. Single bilateral implants or a double bilateral implants filled with progesterone or cholesterol were placed in the ventromedial hypothalamus (VMH) or the preoptic area (POA). Control ewes were not implanted. To determine the inhibitory capacity of the central progesterone implants, ewes received an injection (i.m.) of 8 μg or 16 μg of oestradiol. The single bilateral implants of progesterone failed to block oestrous behaviour and the LH surge induced by 8 μg of oestradiol. Double bilateral progesterone implants in the VMH blocked the sexual behaviour ( P < 0.05) and the LH surge ( P < 0.05), but implants in the POA blocked only sexual receptivity ( P < 0.05). No changes were observed after central implantation of cholesterol. Our results support the hypothesis that progesterone acts centrally in the VMH and the POA to inhibit the induction of LH surge and sexual behaviour by oestradiol.

Inhibition of Sexual Behavior in Male Mice Infected with Taenia crassiceps Cysticerci

Prominent estrogenization and deandrogenization ensue in male mice as a consequence of experimental intraperitoneal infection with Taenia crassiceps cysticerci. The impact of these endocrine changes upon sexual behavior was explored in a group of infected Balb/c male mice at weekly intervals for 15 wk and compared with the behavior of otherwise paired, nonparasitized male mice. Mounting, intromission, and ejaculation responses markedly declined as infection progressed. Six weeks after infection, none of the infected mice displayed ejaculation, the number of mounts and intromissions gradually decreased, and their latencies increased, until, by the 13th wk, none of the parasitized mice showed any sexual response toward female mice. Fifteen weeks after infection, the number of metacestodes per host increased to a couple of thousand, the mean serum estradiol level was approximately 50 times higher than the normal value, and testosterone fell to 5% of its normal level. To fully assess that the inhibition of sexual behavior resulted from the decrease in testosterone levels, a group of 8-wk-infected mice received testosterone, and complete restoration of their sexual behavior was observed. Inhibition of masculine sexual behavior during the infection period is the result of hormonal changes, estradiol being ineffective in maintaining copulation.

Behavioral effects of 3a-androstanediol II: Hypothalamic and preoptic area actions via a GABAergic mechanism

We investigated whether 5a-androstane-3α,17fi-diol (3α-androstanediol; 3α-Diol), a neurosteroid whose effects are primarily inhibitory to sexual behavior, may act through interactions with y-aminobutyric acid (GABA) receptor complexes (GBRs) in the medial basal hypothalamus (MBH) and the preoptic area (POA). In Experiment (Exp.) 1, ovariectomized (ovx) rats were implanted with bilateral guide cannulae aimed above the MBH and were later treated with 17/3-estradiol (E 2, 2 injections of 1 μg/0.2 ml in 10% ethanol) and either 3α-Diol (3.0 mg/kg, s.c.) or vehicle. Progesterone (0.5 mg, s.c.) was given 24 h after the first E2 injection and a pre-test for lordosis responsiveness was carried out 4 h later. The GABA A agonist, muscimol (50 ng), then was infused into the MBH and rats were tested 10, 30 and 60 min later. Muscimol infusion facilitated lordosis behavior in vehicle-treated controls, but 3α-Diol-treated animals failed to show this facilitation. To ascertain whether 3a-Diol would also prevent muscimol's action in the POA, a site in which muscimol inhibits, rather than facilitates, sexual receptivity, ovx animals in Exp. 2 were implanted with bilateral guide cannulae aimed above the POA and were treated with E 2, 3α-Diol, and P and infused and tested as in Exp. 1. Muscimol and 3a-Diol each significantly inhibited receptivity; when they were combined, the inhibition was more pronounced. In Exp. 3, POA infusions of the GABA A antagonist, bicuculline, counteracted muscimol's and 3α-Diol's inhibition of sexual behavior. In Exp. 4, in vitro treatment of POA and MBH membrane fractions with 3α-Diol (30 μM) enhanced maximal [ 3H]muscimol binding without altering the affinity of the binding sites for the agonist. These data suggest that 3α-Diol inhibits E 2 and progest-ininduced lordosis behavior via actions at the GBR in both the MBH and POA.

Male sexual behaviour not abolished after medial preoptic lesion in adult rats

N-methyl-D-aspartic acid (NMDA) was injected into the medial preoptic area (mPOA) of 10 rats to destroy the neurones in this region. Male sexual behaviour was scored before, and on days 2, 6, 10, 17, 24 and 31 after the administration of NMDA. The neurones in the injection site were destroyed in all the rats, but male sexual behaviour was only transiently reduced in the animals with lesions largely restricted to the mPOA. These findings are in contrast to the earlier reports of permanent suppression of sexual behaviour after electrolytic lesion, with damage to the neurones and fibres of passage. The present study shows that the mating behaviour could be expressed even after the destruction of the neurones in the mPOA.

Endotoxin produces a depressive-like episode in rats

Activation of the immune system produces psychological and physiological effects, which resemble the characteristics of depression. The present study was designed to investigate further, in rats, the similarity between the behavioral effects of immune activation and a model of depression in animals. Reduction in the preference for and consumption of saccharin solutions and suppression of sexual behavior were used as models of one essential feature of depression, the inability to experience pleasure (anhedonia). Other measures testing this model were the reduction in food consumption, body weight, locomotor activity, and social interaction. It was found that systemic injection of lipopolysaccharide (endotoxin), which is a potent activator of the immune system, significantly decreased saccharin preference in fluid-deprived rats. Lipopolysaccharide (LPS) also decreased free consumption of saccharin, but not water, in non-deprived rats. Several indices of male sexual behavior were significantly suppressed following LPS administration. Chronic, but not acute, treatment with the tricyclic antidepressant imipramine abolished the suppressive effect of LPS on saccharin preference. Moreover, chronic, but not acute, treatment with imipramine also reduced and facilitated the recovery from the suppressive effects of LPS on food consumption, body weight, social interaction and activity in the open-field test. The results suggest that activation of the immune system in rats produces anhedonia and other depressive-like symptoms, which can be attenuated or completely blocked by chronic treatment with an antidepressant drug.

Levels of Plasma Corticosterone and Testosterone in Male Copperheads (Agkistrodon contortrix) Following Staged Fights

Fighting behavior between male copperheads (Agkistrodon contortrix) occurs during the two mating periods (late summer/fall and spring) to gain priority of access to females. Fights are characterized by prominent vertical challenge displays, swaying, and a high degree of physical contact that does not involve biting. At the moment of subordination, losers retreat quickly from fights and winners respond by chasing. Subsequently, losers do not participate in further challenge displays or fighting for at least 7 days, and also they show behavioral signs of stress, which includes submissive acts and suppression of sexual behavior. The goal of this study was to determine whether or not losers show elevated levels of plasma corticosterone (B) and depressed levels of plasma testosterone (T) relative to winners and controls. Winners and losers were produced in 13 staged trials. Two different controls (N= 26) were run. Males with no recent agonistic experience were (1) tested in the fighting arena in the absence of a competitive male but paired with a single female (N= 13), and (2) tested alone in their cages (N= 13). All trials, including controls, were conducted in spring and late summer. Mean B in losers at 1-hr postfight was significantly greater than in winners and both control groups in both seasons. Mean T was significantly greater in late summer in all groups, as expected, but in each season was not significantly different between the groups. Levels of B and T were not correlated with SVL, mass, or duration of fighting. This study provides further support for the social insensitivity/challenge hypotheses and is the first to document postfight B and T levels in snakes.

Behavioural and endocrine predictors of dominance and tolerance in female common marmosets, Callithrix jacchus

As a result of social subordination, female common marmosets undergo suppression of ovulation and inhibition of sexual behaviour. This study examined the possibility that subordination also results in decreased aggressiveness and increased submissiveness towards same-sex strangers. Thirty-two adult females were pre-assigned to eight mixed-sex social groups. The females' behavioural and adrenocortical responses to brief confrontations with each of three female strangers were assessed under two conditions: while subjects were pair-housed with a male and while they were living in established, mixed-sex groups. Only 22% of subjects threatened stimulus females in the heterosexual pairs condition, 47% submitted and 31% showed no agonism. These agonistic behaviour patterns reliably predicted whether a female would become dominant or subordinate in a mixed-sex group. When animals were housed in established social groups, both dominant and subordinate females either showed similar responses to stimulus animals as they did in the earlier condition or became somewhat less responsive. Plasma cortisol levels did not correlate with agonistic behaviour and were not elevated by stranger-encounter testing. Finally, in the first 10 days following group formation, subordinate females that had shown ovulatory cyclicity prior to group formation were significantly more likely to receive persistent aggression from their dominant female groupmate than subordinates that had been anovulatory. These results suggest that attainment of social status between female marmosets is closely related to pre-existing individual differences in agonistic behaviour, whereas tolerance between females depends upon ovarian function.

Fighting dynamics of male copperheads,Agkistrodon contortrix (Serpentes, Viperidae): Stress-induced inhibition of sexual behavior in losers

Adult male copperheads (Agkistrodon contortrix) fight for priority of access to females during the mating periods in spring and late summer. During fights, one male abruptly quits and retreats, and the other chases in pursuit. One male thus emerges as the winner and the other as the loser. Reversal of this outcome does not occur during the time of observation (30 min) nor in 24 hr postfight trials. In all cases, winners gain priority of access to females. Losers, in contrast, do not pursue females nor gain access to them, even when winners are removed from the arena. In this study, courtship performance of male A. contortrix was studied in the laboratory using subjects with either winning or losing experience from staged fights. All males used first were tested with a single female to determine courtship performance prior to the agonistic trials. From these tests, each male was given a single courtship score of 0 (no courtship) to 3 (most intense courtship). Only males receiving a score of 2–3 were used in the initial agonistic trials. All staged fights were conducted in a large arena and involved two males and one female. Following fights, winners and losers were tested again for courtship performance. In trials conducted at 24 hr and 7 days postfight, only losers were tested. It was found that prefight courtship scores were not significantly different between winners and losers. At 30 min postfight, most losers showed complete suppression of courtship behavior (score 0). Winners, in contrast, showed equivalent or an increase in their courtship scores. At 24 hr postfight, courtship scores of losers remained significantly lower than their prefight scores. At 7 days postfight, courtship scores of losers were not significantly difference from their original prefight scores. Fighting behavior in free-ranging A. contortrix represents a potentially significant cost to losers if it is associated with loss of reproductive opportunities. Recent evidence from hormonal studies indicates that inhibition of courtship and fighting behavior in male A. contortrix is stress-induced. © 1996 Wiley-Liss, Inc.

Induction of mating behavior by apomorphine in sexually sated rats

We have tested the hypothesis, suggested by our previous neurochemical studies, that the inhibition of sexual behavior that follows unrestricted mating could be caused by a blockade of dopaminergic transmission. Male rats were allowed to copulate until they reached a satiety criterion. The following day, after verification that they were sexually inactive, the animals were injected with the dopamine agonist, apomorphine, at doses of 80, 200, and 500 μg/kg body weight and their behavior with receptive females was recorded. A bell-shaped dose-response curve was found, with the 200 μg/kg dose having the maximal stimulatory effects on mating. Whereas these findings seem to support the above hypothesis, it should be noted that apomorphine treatments were unable to restore fully the copulatory pattern shown by sexually rested animals. This could be due to several factors including the interference of apomorphine-induced stereotypies, and/or the involvement of additional transmitter systems in the mechanisms of sexual satiety.

The inhibition of sexual behavior in male rats by propranolol is stereoselective

We have previously reported that administration of racemic mixtures of propranolol was associated with a marked inhibition of mating behavior in male rats. To compare the effects of (+)-propranolol, (−)-propranolol, and (±)-propranolol in sexually experienced males, rats ejaculating in four or more mating tests were divided into three groups ( N = 16 per group) such that no differences in parameters of copulatory behavior were evident in preexperimental tests. No major effect of propranolol on parameters of behavior associated with initiation of sexual behavior was evident. In contrast, other measures of behavior were profoundly modified. The ejaculatory threshold, indicated by the number of intromissions preceding ejaculation, was increased after (+)- and (±)-propranolol, but not (−)-propranolol. The number of mounts without intromission preceding ejaculation was increased only after (±)-propranolol. A decrease in copulatory efficacy was evident after (−)- or (±)-propranolol, but not after (+)-propranolol. Increases in ejaculation latency, intercopulatory interval, and postejaculatory interval were observed after (−)- and (±)-proranolol, but not after (+)-propranolol. In summary, the present data indicate that the (−) isomer of propranolol is the active form necessary for the inhibitory effects of propranolol on male sexual function. We suggest that this inhibition is due to specific receptor-mediated mechanisms, involving β-adrenoceptors and 5-HT 1A receptor interactions.

C- fos expression in the rat brain following central administration of neuropeptide Y and effects of food consumption

Administration of neuropeptide Y (NPY) intracerebroventricularly (i.c.v.) results in the release of a number of hypothalamic and pituitary hormones and stimulation of feeding and suppression of sexual behavior. In this study, we sought to identify cellular sites of NPY action by evaluating perikaryal Fos-like immunoreactivity (FLI), a marker of cellular activation, in those hypothalamic and extrahypothalamic sites previously implicated in the control of neuroendocrine function and feeding behavior. Additionally, we compared the topography of FLI in these brain sites when food was either available ad libitum or withheld after NPY injection (1 nmol/3 μl, i.c.v.). The results showed that one hour after NPY injection a large number of cells in the parvocellular region of the paraventricular nucleus (PVN) were FLI-positive in the absence of food consumption. However, in association with food intake, a significant number of cells were intensely stained in the magnocellular region of the PVN. An analogous increase in FLI in association with feeding was apparent in the supraotic nucleus (SON), the dorsomedial nucleus and the bed nucleus of the stria terminalis in the hypothalamus. Anong the extrahypothalamic sites, feeding facilitated FLI in a large number of cells located in the lateral subdivision of the central amygdaloid nucleus and the lateral subdivision of the solitary tract. FLI was observed in a moderate number of cells in the hypothalamic arcuate nucleus (ARC) and ventromedial nucleus, and this response was not changed by feeding. Cumulatively, these results show that neurons in a number of discrete hypothalamic and extrahypothalamic sites, previously implicated in the control of neuroendocrine function and feeding behavior, are activated by NPY and further, a divergent pattern of c-fos expression emerged in some of these sites if feeding occurs after NPY injection. Stimulation of FLI in cells of the PVN, SON and ARC by NPY imply the presence of NPY target cells that play a role in the neuroendocrine control of pituitary function. The finding that NPY induced FLI in cells located in the parvocellular subdivision of the PVN even in the absence of feeding, imply that cells involved in initiation of food intake by NPY may reside in this subdivision of the PVN. On the other hand, the appearance of Fos-cells in the magnocellular subdivision of the PVN in response to feeding, suggests neural mechanisms that operate during the post-ingestion period, including those associated with termination of NPY-induced feeding, may impinge upon this subdivision of the PVN.

Corticotropin‐releasing factor: an antireproductive hormone of the testis

Corticotropin-releasing factor (CRF), the key neuropeptide in the stress cascade, has major inhibitory actions on testicular function in addition to its known antireproductive effects at the central level (inhibition of sexual behavior and LH secretion). CRF is secreted by the Leydig cells of the testis and acts through high-affinity receptors at the Leydig cell membrane as a potent negative regulator of LH action, inhibiting gonadotropin-induced cAMP generation and androgen production. CRF is also a primary stimulus of beta-endorphin secretion by the Leydig cells, which in turn exerts paracrine inhibition of FSH action in the tubular compartment of the testis through high-affinity receptors in the Sertoli cells. CRF action in the Leydig cells involves a pertussis toxin-insensitive guanyl nucleotide regulatory unit. In contrast to CRF receptors in the brain, pituitary, and other peripheral tissues, those in the Leydig cell are not coupled to Gs. The inhibitory action of CRF in the Leydig cell is exerted through protein kinase C, at the level of the catalytic subunit of adenylate cyclase. The secretion of CRF by the Leydig cell is stimulated by LH, acting via release of serotonin (5HT) and autocrine activation of 5HT2 receptors. Serotonin acts on 5HT2 receptors in the Leydig cell to stimulate CRF secretion via a pertussis toxin insensitive G-protein and presumably through activation of phosphoinositide hydrolysis. The diversity of the biochemical responses to CRF and 5HT2 receptor activation (i.e., inhibition of adenylate cyclase at the cytoplasmic aspect of the cell membrane vs. stimulation of CRF release from secretion granules) may reflect the stimulation of different protein kinase C isoenzymes. The LH-->5HT-->CRF inhibitory loop serves to continuously buffer the stimulation of androgen production by gonadotropin. 5HT, the immediate stimulus of testicular CRF secretion, is released during stress and is locally increased in the testis in pathological conditions associated with impaired testicular function (i.e., orchitis, varicocele). Also, propranolol, the beta-adrenergic antagonist frequently used in the control of blood pressure in patients with hypertension and often associated with impotence, acts via a serotonergic mechanism to stimulate CRF secretion and causes marked inhibition of LH-induced cAMP production and steroidogenesis in cultured Leydig cells. These basic studies of 5HT and CRF are relevant to the pathogenesis of testicular dysfunction and for the development of antagonist therapies to block CRF production and its local antireproductive effects.

Intracerebral actions of the 5-HT 1A agonists, 8-OH-DPAT and buspirone and of the 5-HT 1A partial agonist/antagonist, NAN-190, on female sexual behavior

Proestrous rats were infused intracerebrally with 50–1000 ng 8-OH-DPAT, 500 or 2000 ng buspirone or 125–500 ng NAN-190. For each drug, bilateral infusions into the mediobasal hypothalamus inhibited female lordosis behavior and proceptivity and initiated resistive behavior. The effects of the drugs were evident within 5–20 min of infusion and generally lasted for 1–2 hr. The effective sites for 5-HT 1A-mediated inhibition of sexual behavior were most concentrated in the ventromedial nucleus of the hypothalamus. Cannulae sites anterior, posterior or dorsal to the ventromedial nucleus or clearly within the IIIrd ventricle were less effective at disrupting lordosis behavior. The inhibition of sexual behavior, following 8-OH-DPAT occurred in a dose-dependent manner and appeared to include the loss of motivation of the female to mate. Buspirone produced similar, but quantitatively smaller, effects on lordosis behavior. NAN-190 slightly, but significantly, suppressed lordosis behavior after either intracerebral or intraperitoneal injection and substantially increased resistive behavior. These results suggest that the inhibition of lordosis behavior, following treatment with 5-HT 1A agonists, include an action within the ventromedial nucleus. Moreover, 5-HT 1A receptors in this area appear to play a functionally important role in the modulation of the female's “willingness” to mate.

Inhibitory effect of opiates on male rat sexual behavior may be mediated by opiate receptors outside the central nervous system.

The importance of opiate receptors outside the central nervous system for the inhibitory actions of morphine on male rat sexual behavior was evaluated. Morphine (10 mg/kg) produced an almost complete inhibition of sexual behavior. This inhibition was antagonized by naloxone at a dose of 1 mg/kg but not at a dose of 0.25 mg/kg. The quaternary opioid antagonist methylnaloxone effectively blocked the inhibitory actions of morphine at a dose of 20 mg/kg but not at a dose of 5 mg/kg. Since the affinity of methylnaloxone for opiate receptors is about 5% of that of naloxone, it may be concluded that both antagonists were about equally effective in inhibiting the effects of morphine. Furthermore, the opiate-like drug loperamide was found to inhibit sexual behavior. This drug acts mainly outside the central nervous system. Its effect was blocked by both naloxone and methylnaloxone, suggesting that opiate receptors are involved. It was also shown that methylnaloxone is unable to block the reinforcing effects of morphine in the conditioned place preference procedure. Because the reinforcing effects of opiates seem to be localized to the central nervous system, it may be proposed that methylnaloxone does not antagonize morphine's central effects. Moreover, loperamide had no effect in the place preference procedure, suggesting that this drug does not act at central opioid receptors. Taken together, these data show that peripheral opioid receptors are responsible for at least some of the inhibitory actions of morphine on male sexual behavior. After treatment with morphine + methylnaloxone, ejaculatory mechanisms were facilitated, reflected in a reduced number of preejaculatory intromissions and a shortened ejaculation latency.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of non-competitive NMDA receptor antagonists on reproductive and motor behaviors in female rats

MK-801 and dextrorphan, selective non-competitive antagonists atN-methyl- d-aspartate (NMDA) receptors, were used to evaluate the effect of NMDA receptor blockade on sexual and motor behaviors in female rats. Ovariectomized rats were treated with estradiol benzoate (EB) for 48 or 72 h followed by progesterone (P) 3.5–4 h before testing the animals for sexual receptivity. After testing for estrous responsiveness, the effect of NMDA antagonists on several motor behaviors was also assessed. Lordosis frequency and intensity were inhibited in animals that received 0.5 mg/kg MK-801 30 min before EB; the same dose of MK-801 was relatively ineffective when administered 24 h after EB. In neither case did MK-801-treated females differ from controls when motor behaviors were assessed after mating tests. When 30 mg/kg dextrorphan, a short-acting NMDA antagonist, was administered 15 min before P, sexual behavior was not blocked. However, both 0.05 mg/kg MK-801 and 30 mg/kg dextrorphan suppressed ongoing female sexual behavior within 30 min in animals made receptive with EB and P. These deficits in sexual behavior were associated with changes in motor performance. MK-801 (0.1 mg/kg) and dextrorphan (30 mg/kg) abolished movement in the vertical dimension (e.g. jumping and rearing). By contrast, the drugs increased movement in the longitudinal (locomotion) and lateral (circling) dimensions. At 0.2 mg/kg, MK-801 blocked movement in both the vertical and longitudinal dimensions; however, it failed to block circling. Only at 0.4 mg/kg did MK-801 inhibit lateral movements and righting reflexes. It is likely that the acute inhibition of sexual behavior by NMDA antagonists is related to changes in sensorimotor processing and/or motor performance.

Effects of the 5-HT 1A agonist, 8-OH-DPAT, on sexual behaviors of the proestrous rat

The effects of the 5-HT 1A agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), were examined in intact, proestrous rats. Although this compound has been reported to inhibit sexual receptivity of hormonally primed, ovariectomized rats, this is the first report of its effect in intact females. After intraperitoneal treatment with 8-OH-DPAT (0.01 to 0.25 mg/kg), there was a dose-dependent suppression of lordosis behavior. The inhibition occured within 10–15 min after the higher doses and lasted at least an hour after treatment. When females were treated with 1 mg/kg trifluoromethylphenyl piperazine (TFMPP) 30 min prior to treatment with 0.1 mg/kg 8-OH-DPAT, females recovered more rapidly from the inhibitory effects of 8-OH-DPAT. After bilateral, intrahypothalamic infusion of 50 to 1000 ng 8-OH-DPAT, inhibition of sexual behavior resembled that seen following systemic treatment. Cannula locations in the ventromedial hypothalamus, but not the posterior hypothalamus, produced rapid inhibition of lordosis behavior. Both the frequency and the quality of lordosis behavior were reduced within 5 to 10 min after bilateral infusion of 200 to 1000 ng (but not 50 ng) 8-OH-DPAT, and females often succesfully avoided attempted mounts by the male. These results suggest that activation of ventromedial hypothalamic 5-HT 1A receptors reduces lordosis behavior.

Determination of Enkephalins in Rat Cerebrospinal Fluid with High‐Performance Liquid Chromatography‐Electrochemical Detection: Increased Concentrations During Lactation are Controlled by Sucking

Abstract Methionine- and leucine-enkephalin were measured in the cerebrospinal fluid of lactating rats by high-performance liquid chromatography and electrochemical detection. The concentration of both peptides was high while the rats were nursing their litter. The concentration of methionine-enkephalin decreased rapidly when the mother left her litter and increased equally rapidly after mother-young reunion, provided the pups were allowed direct contact with the nipples of the mother. The level of leucine-enkephalin did not change during the period of time the lactating rat normally stayed away from its litter but decreased after prolonged (12 h) mother-pup separation. These results show that the concentration of methionine-, but not leucine-enkephalin in the cerebrospinal fluid fluctuates as the lactating rat interacts with its litter and is directly dependent upon the suckling stimulus. Although methionine-enkephalin may contribute to the inhibition of sexual behaviour which occurs during lactation, the role of the enkephalins in the other behavioural and endocrine adaptations of lactation is unknown.