Anteromedial hypothalamic lesions block proceptivity but not receptivity in the female common marmoset (Callithrix jacchus)

The sexual behavior of 8, estradiol-treated, ovariectomized common marmosets was recorded prior to and after bilateral radiofrequency lesions of the hypothalamus. Lesions of the anterior hypothalamus, which extended to varying degrees into the medial hypothalamus, virtually abolished proceptive tongue-flicking and staring displays. Tongue-flicking during copulation also decreased, but the females did not show any significant increase in the number of mounts which they refused or terminated with the exception of one animal which had received more extensive damage to the medial hypothalamus. Significant increases in the frequencies of allogrooming and grooming invitations also occurred after the females had been lesioned. Sexual behavior was not significantly altered in 3 females which received sham lesions. These results provide the first direct evidence for a neuroanatomical distinction between hypothalamic mechanisms which regulate proceptivity and receptivity in primates.     

Ibotenic acid-induced lesion of the peripeduncular area does not impair the lordosis reflex in the cyclic female rat

In the ovariectomized, hormone-primed rat the peripeduncular area (PPA) has been reported to play a key role in sexual receptivity by integrating the sensory and endocrine inputs necessary for the elicitation of the lordosis reflex. The present study was undertaken to investigate the effect of bilateral peripeduncular lesions induced by ibotenic acid on the lordosis behavior of the normal, cyclic rat. Sexually unexperienced females received a bilateral microinjection of either ibotenic acid (n = 14; lesion group) or phosphate buffer (n = 8; sham-operated group) in the PPA. Following recovery, the receptivity expressed as the lordosis quotient was controlled in the presence of a sexually active male. The results indicate that in both groups the females display a high lordosis quotient (LQ greater than 90%). Therefore, in the cyclic female rat, the manifestation of sexual receptivity does not seem to be affected following bilateral destruction of the PPA.     

Effects of hypothalamic lesions upon the sexual and social behaviour of the male common marmoset (Callithrix jacchus)

The sexual and associated behaviour of 10 adult male marmosets was recorded during pair tests with ovariectomized females, before and after bilateral thermal lesions of the hypothalamus. Four sham-lesioned males served as controls. Lesions varied in volume from 1.49 to 3.28 mm³ and extended from the ventromedial hypothalamus to the diagonal band of Broca. Precpulatory behaviours (anticipatory erections, tongue flicking and anogenital investigations of the female) as well as frequencies of mounting, intromission and ejaculation decreased in lesioned males. The greatest suppression of sexual behaviour occurred after lesioning the anterior hypothalamus (AH), beneath the anterior commissure, or at the junction of the AH with the preoptic area (POA). Lesions confined to the POA had less profound behavioural effects. Treating ovariectomized females with estradiol stimulated their proceptivity but had no consistent effects upon the male's behaviour. Lesioned males did not exhibit signs of social withdrawal and frequencies of allogrooming or grooming invitations increased post-operatively. Preliminary studies on intermale aggression indicated that lesions which had he greatest effect upon sexual behaviour also tended to decrease aggressive interaction with other males. Hypothalamic lesions did not affect plasma testosterone levels, except in one male and only one animal showed signs pf ill health (weight loss and hypothemia) post-operatively. These results show that damage to the AH or AH-POA junction in male marmosets causes a profound suppression of sexual ‘arousal’ and copulatory behavior and that such affects are not due to androgen insufficiency or other, non-specific, side effects of neural damage.     

Ventromedial hypothalamus as a target for oestradiol action on proceptivity, receptivity and luteinizing hormone surge of the ewe

Most of the literature suggests that in sheep as in rodents nervous structures involved in female sexual behaviour are not necessarily identical to those involved in the LH surge. In rodents, oestradiol triggers female sexual behaviour by acting on a restricted area of the mediobasal hypothalamus whereas the concomitant induction of the preovulatory LH surge is at least partially under the control of more anterior structures. The central sites of oestradiol action, however, remained poorly defined in sheep. To provide this definition, 37 ovariectomized ewes were stereotaxically implanted unilaterally or bilaterally with a guide cannula in preoptic area (POA), anterior, mediobasal, lateral, or posterior hypothalamus (AH, MBH, LHT, PH). Experiments were made during the breeding season (Br) and the anoestrous period (An: unilat only) and females were primed with a peripheral treatment of progesterone and a dose of 17 beta-oestradiol subthreshold for both the LH surge and sexual behaviour. Intracranial implants (i.d. = 0.45 mm) of crystalline E2 were lowered 16 h after progesterone removal and left in the brain for 48 h. Whereas POA implants never had any significant effects on either the behaviour or the LH surge, all MBH implants caused receptivity (11 bilat, 5 unilat Br and 5 unilat An). Bilateral MBH implants also induced proceptivity in 9 of 11 ewes and increased the LH levels in 7 of them. These proportions do not differ significantly from those observed after a 25 microgram peripheral injection of E2. Unilateral MBH implants had no significant effect on proceptivity and LH increase but oestrous behaviour was induced by some implants placed laterally to the MBH (25 recept and 3/5 procept).(ABSTRACT TRUNCATED AT 250 WORDS)     

Interactions between oestradiol and the progesterone antagonist RU-486 in establishing and maintaining female rats' sexual responsiveness: central versus peripheral effects.

Progesterone is well known to contribute specifically to the emergence of the female rats' sexual behaviour by the establishment of 'proceptivity'. Analysis of the mechanism of progesterone action benefits from the availability of highly effective anti-progestagenic compounds. However, results obtained during the study of female rats' sexual behaviour, including such compounds into the experimental protocol, appear equivocal. The present experiments were designed to further examine the possible effects of the antiprogestagenic compound RU-486 (Mifepristone) on the female rats' sexual responsiveness as elicited through exposure of the animals to oestradiol alone. The experimental design aimed to distinguish between receptivity (defined as response to sexually active males) and proceptivity (defined as female-initiated sexual behaviour). Mifepristone advanced the onset of receptivity after the injection of oestradiol benzoate (OB). Upon further investigation a steady level of receptivity was reached during prolonged treatment with OB and this level appeared unaltered through concurrent treatment with Mifepristone. OB alone was insufficient to induce full proceptivity as revealed by observations of sexual behaviour with tethered males. Such defined proceptivity was significantly further inhibited by Mifepristone. It thus appears that, dependent upon the time and type of female sexual behavioural analysis, Mifepristone either enhances, inhibits, or does not affect sexual responsiveness. After the observation period, autopsy revealed the presence of copulatory plugs and infections in the uterus of OB + Mifepristone-treated rats. This unexpected finding could result from effects of the compound on the uterine cervical musculature. Uterine infections might result in painful, aversive, intra-abdominal sensations, especially during intravaginal penile intromissions.(ABSTRACT TRUNCATED AT 250 WORDS)     

Involvement of serotonin and γ-aminobutyric acid in the timing of estrous receptivity in the cyclic female rat

The involvement of serotonin (5HT) and γ-aminobutyric acid (GABA) in the control of estrous sexual receptivity has been investigated in the cyclic female rat. (1) When injected at 1300 hr on proestrus parachlorophenylalanine (pCPA) specifically increased sexual receptivity as expressed by the number of receptive females between 1800 and 1900 hr and simultaneously depressed 5HT turnover. (2) A specific decrease in blood progesterone (P) concentration was observed on proestrus at 1530 hr in females treated with pCPA on proestrus at 1300 hr. (3) When injected on proestrus at 1730 hr dipropylacetate (DPA) induced a decrease in sexual receptivity between 1830 and 1900 hr in both intact and bulbectomized females but it depressed the lordosis quotient only in unoperated females. (4) An increase in the amount of γ-aminobutyric acid (GABA) in the olfactory bulbs and in the hypothalamus was noted at 1845 hr in DPA treated females. A significant decrease in the olfactory bulb GABA content occurred from 1845 to 2245 hr on proestrus. (5) The results are in favor of an involvement of 5HT and GABA in the control of the timing of sexual receptivity by the olfactory bulbs in the rat. They also suggest that interactions between P and 5HT are implicated in the control of sexual receptivity in the cyclic female rat.     

The effects of implanting testosterone propionate into the central nervous system on the sexual behaviour of adrenalectomised female rhesus monkeys.

Bilateral adrenalectomy rendered ovariectomised, oestrogen-treated female rhesus monkeys sexually unreceptive. Small unilateral implants of testosterone propionate (mean weight 140 mug) into the anterior hypothalamus/preoptic area restored receptivity in 7 out of 8 of these monkeys. Cholesterol implanted into the same area, or similar amounts of testosterone propionate implanted into the posterior hypothalamus/pretectal area (4 females) or cerebral cortex/dorsal thalamus (5 monkeys) had no consistent effect on behaviour. It therefore seems likely that androgens regulate sexual receptivity in female monkeys by acting on some part of the anterior hypothalamus. Thus, though the hormonal control of receptivity in female primates differs from non-primates, the site on which hormones act to regulate this behaviour may be similar in both.     

Participation of the lateral midbrain tegmentum in the neuroendocrine control of sexual behavior and lactation in the rat

Electrolytic lesions were placed in the ventrolateral midbrain and their effects on lactational performance and sexual behavior were assessed. The neuronal injury, situated just above the lateral tip of the substantia nigra in the lateral tegmentum, caused an immediate impairment in lactational performance as measured by the weight gain of the offspring, and interfered also with the hormonal induction of sexual receptivity and proceptivity. In similarly lesioned male rats, mounting behavior was virtually absent, but nociceptive thresholds and locomotor activity in the open-field remained unaltered. It seems likely that some, but not all, of these effects were due to disruption of a pathway carrying somatosensory information relevant for lactation and sexual behavior.     

Lesions in the preoptic area suppressed sexual receptivity in ovariectomized rats with estrogen implants in the ventromedial hypothalamus

The objective of the experiment was to determine if electrolytic ablation of a portion of the preoptic area (POA) influenced the activation of female lordosis behavior by implants of estradiol benzoate in the ventromedial hypothalamus (VMH) of ovariectomized (OVX) rats. Two weeks after ovariectomy, rats received either bilateral electrolytic lesions (2 mA for 10 sec in Experiment 1, or 1 mA for 5 sec in Experiment 2) in the POA, or sham lesions (all procedures except passage of current). On the same day (day 0 of the experiment) thirty-gauge stainless steel cannulae containing crystalline estradiol benzoate were stereotaxically placed bilaterally into the VMH of all the rats. Subsequently, females were tested for the lordosis response to stud males on days 2, 4, 6, 8, and 10 in Experiment 1 or on days 7, 14 and 15 in Experiment 2. All rats received 0.5 mg progesterone (SC) only before the last test. A female was considered sexually receptive if she exhibited a lordosis quotient (LQ) greater than or equal to 10 (LQ = No. lordosis responses/10 mounts by male X 100). The frequencies for sexual receptivity in females with POA lesions were significantly lower than those for control females without lesions in both experiments. Additionally the degree of receptivity (lordosis quotient) was significantly lower on each test day for rats with POA lesions than that for rats without POA lesions. The results imply that the maintenance of the integrity of the POA under this experimental condition was important for the expression of the facilitative influence of the VMH on lordotic responsiveness.     

On the role of the dorsal mesencephalic tegmentum in the control of masculine sexual behavior in the rat: Effects of electrolytic lesions, ibotenic acid and DSP4

The work presented here concerns the way in which the dorsal midbrain tegmentum (DMT) participates in the control of sexual behavior. It was first established that electrolytic DMT lesions accelerate mating in the male rat, primarily by abbreviating the post-ejaculatory interval. Since the effective lesions were accompanied by decreases in the in vitro synaptosomal uptake of [³H]noradrenaline (NA) in hippocampus and hypothalamus, the behavioral effects of DSP4 (which elicits degeneration in NA nerve terminals derived primarily from the locus coeruleus) were examined. The long-term behavioral consequences of DSP4, however, were to decrease copulatory rate despite substantial NA denervation of brain and spinal cord. Ibotenic acid-induced neuronal degeneration in the DMT, on the other hand, accelerated copulatory behavior while leaving NA innervation of hippocampus and hypothalamus unaffected. The magnitude of the behavioral effect in ibotenic acid-treated rats was less than that induced by electrolytic DMT lesions. It is tentatively suggested on the basis of these experiments that DMT cell bodies may form part of a system regulating sexual arousal mechanisms, whilst activity in a non-adrenergic fiber system running in the dorsal tegmental bundle may be required for active inhibition of sexual behavior after ejaculation.

In additional experiments it was found that DSP4 treatment of female rats produced negligible effects on sexual behavior, estrous cyclicity and processes related to lactation.     

The effects of excitotoxin lesions of the lateral hypothalamus on self-stimulation reward

Unilateral microinjection into rat lateral hypothalamus (LH) of the excitotoxins ibotenic acid (IBO) and N-methyl-D-aspartic acid (NMDA) produced a local zone of neuronal death but also produced a zone of demyelination. The size of this demyelination zone was related to excitotoxin dose and was smaller than the zone of neuron killing. In behavioral testing, MFB self-stimulation reward and performance were measured with a rate-frequency curve-shift method before and after IBO or NMDA lesions of the LH. Excitotoxin lesions were made anterior or posterior to the LH electrode so that the zone of neuronal death, but not demyelination, extended to the electrode tip. These lesions produced small, temporary LH stimulation reward deficits, leading to the conclusion that intrinsic LH neurons are not a major substrate of MFB stimulation reward.     

Steroid implants in the medial preoptic area or ventromedial nucleus of the hypothalamus activate female sexual behaviour in the musk shrew

Female musk shrews are induced ovulators that do not exhibit a spontaneous behavioural oestrous cycle. Testosterone produced by the ovaries and adrenal glands, is the major steroid hormone in circulation at times of mating, and as such, regulates sexual behaviour. In the first experiment, we identified the neural site(s) of action for testosterone. Hormone implants were placed in one of three targeted brain regions. The neural sites selected were the medial anterior division of the bed nucleus of the stria terminalis (BNSTMA), medial preoptic area (mPOA) and the ventromedial nucleus of the hypothalamus (VMN). Ovariectomized females who received a unilateral testosterone propionate implant in either the mPOA or VMN, were significantly more likely to display sexual behaviour as compared to females who received an implant in the BNSTMA or any other hypothalamic nucleus. In experiments 2 and 3, we investigated whether the behavioural effects of testosterone propionate were mediated by an oestrogen receptor or the androgen receptor. Ovariectomized females that received oestradiol (E2) implants in either the mPOA or VMN were more likely to display receptivity, and had significantly shorter behavioural latencies, as compared to females implanted with either dihydrotestosterone or cholesterol. These data show that neural aromatization of testosterone to E2 in the mPOA or VMN is necessary for optimal activation of female musk shrew sexual behaviour. This finding implies a degree of neural redundancy in the networks that control the expression of sexual receptivity.     

Immediate early gene activity‐regulated cytoskeletal‐associated protein regulates estradiol‐induced lordosis behavior in female rats

Sensory feedback is an important component of any behavior, with each instance influencing subsequent activity. Female sexual receptivity is mediated both by the steroid hormone milieu and interaction with the male. We tested the influence of repeated mating on the level of sexual receptivity in ovariectomized rats treated with estradiol benzoate (EB) once every fourth day to mimic the normal phasic changes of circulating estradiol. Females were divided into two groups: naïve, which were tested for lordosis behavior once, and experienced rats, which were tested for lordosis after each EB injection. To monitor the effect of mating, the number of neurons expressing the immediate early gene activity‐regulated cytoskeleton‐associated protein (Arc) were counted in the mediobasal hypothalamus. Females were unreceptive following the first EB treatment, but the mating induced Arc expression. In naïve rats, each subsequent EB injection increased the levels of sexual receptivity. This ramping was not observed in experienced rats, which achieved only a moderate level of sexual receptivity. However, experienced females treated with EB and progesterone were maximally receptive and did not have Arc expression. To test whether the expression of Arc attenuated lordosis, Arc antisense oligodeoxynucleotides (asODN) were microinjected into experienced females' arcuate nuclei. Arc expression was attenuated, and the experienced EB‐treated females achieved maximal sexual receptivity. These results demonstrate that Arc expression in the hypothalamus might influence future sexual receptivity and provides evidence of learning in the arcuate nucleus. The loss of Arc results in unrestrained sexual receptivity. © 2014 Wiley Periodicals, Inc.     

Ibotenic acid-induced lesions of the medial preoptic area/anterior hypothalamus enhance the display of progesterone-facilitated lordosis in male rats

Electrical lesions of the medial preoptic area/anterior hypothalamus (MPOA/AH) have been reported to enhance the display of steroid-induced lordosis in castrated male rats. This study employed the cell body-specific neurotoxin, ibotenic acid, to ascertain whether neurons originating in this region (as opposed to axons of passage) tonically inhibit steroid-induced lordosis in adult male rats. Castrated, adult Long-Evans males received bilateral electrical lesions or injections of ibotenic acid or vehicle aimed at the MPOA/AH. Following administration of estradiol benzoate (EB) and progesterone, lordosis quotients (LQs) and lordosis ratings (LRs) were significantly higher in groups of rats with electrical lesions (LQ= 62.2 ± 15.1;LR= 1.22 ± 0.34) and ibotenic acid-induced lesions (LQ = 58.1 ± 12.2;LR= 0.99 ± 0.24) than in the control group (LQ= 12.8 ± 7.3;LR= 0.22 ± 0.13). To determine whether this enhancement of receptive behavior in MPOA/AH-lesioned males was an effect on estradiol-induced, as compared to progesterone-facilitated lordosis, groups of castrated rats in a second experiment received bilateral injections of ibotenic acid or vehicle aimed at the MPOA/AH and were tested for lordosis after administration of EB alone and again after injection of progesterone. Following treatment with EB alone, rats with ibotenic acid-induced MPOA/AH lesions tended to be slightly less receptive than control animals. However, following injections of progesterone, LQs and LRs were higher in the MPOA/AH-lesioned group than in the control animals, as had been observed in the first experiment. These data are consistent with the hypothesis that cell bodies, rather than axons of passage, originating in the MPOA/AH exert tonic inhibitory control over the display of progesterone-facilitated lordosis in adult male rats.     

Inhibition of sexual receptivity after intracranial cycloheximide infusions in female hamsters

Female hamsters were ovariectomized and one week later stereotaxically infused with 20 micrograms cycloheximide (20 micrograms/microliter, 0.6 microliter/min) or 1 microliter saline bilaterally into one of several brain sites. Thirty min after the infusion, the animals were injected with 5 micrograms estradiol benzoate (EB) then 44 hr later with 500 micrograms progesterone and tested with a male for receptivity at hour 48. One week later the animals were retested with EB and progesterone but without any intracranial infusion to investigate the possibility of permanent lesion effects. The greatest inhibition of receptivity occurred in females which received cycloheximide in the ventromedial hypothalamus (VMH) or lateral to the VMH. Saline infusions into the VMH had no inhibitory effects. Inhibition was rarely seen after infusion into the preoptic area, anterior hypothalamus, dorsomedial hypothalamus, cortico-medial amygdala, or septal area. Moderate inhibition was found after infusion of cycloheximide into the third ventricle. The inhibition following cycloheximide infusion was not permanent or irreversible. On the retest one week later the animals were sexually receptive. These results suggest that protein synthesis within the VMH is an essential part of the initial action of estrogen for the induction of sexual receptivity in hamsters.     

The influence of corticosterone on serotonergic stereotypy and sexual behavior in the female rat

The effects of adrenalectomy and chronic corticosterone treatment on sexual behavior in the ovariectomized female rat were investigated. The serotonergic type 2A (5-HT2A) receptor-mediated behavior 'wet dog shakes' (WDS) was measured concurrently. In Experiment 1, adrenalectomy reduced the frequency of WDS following the administration of the 5-HT(2A/2C) receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) but had no effect on spontaneous WDS. In Experiment 2, chronic corticosterone treatment increased DOI-induced WDS in both adrenalectomized and sham-adrenalectomized rats. In Experiment 3, adrenalectomized and sham-adrenalectomized rats were compared on measures of spontaneous WDS and sexual behavior following the administration of estrogen alone, or estrogen in combination with progesterone. Chronic corticosterone and acute progesterone administration increased WDS and facilitated sexual receptivity and proceptivity, while adrenalectomy decreased WDS, facilitated sexual receptivity and inhibited proceptivity. These findings suggest that the behavioral effects seen following hypothalamic-pituitary-adrenal (HPA) axis disruption may, in part, be mediated by altered 5-HT2A receptor responsivity.     

Comparison of electrolytic and ibotenic acid lesions in the lateral hypothalamus

Electrolytic lesions in the lateral hypothalamus (LH) seriously affect ingestive behavior and sensorimotor functions in the rat. We here report that bilateral infusions of the neurotoxin, ibotenic acid (IBO) in the LH yield a decrease in body weight, but not to the same extent as electrolytic lesions. The sensorimotor impairments were most severe after electrolytic lesions. When tested in a residential maze on days 5-7 and 18-20 after surgery, both lesioned groups showed no lack of motivation to seek food and water. Histological examination of the LH following IBO exposure revealed extensive degeneration of neuronal cell bodies with little evidence of non-specific damage. Biochemical analysis of the rostral forebrain content of norepinephrine (NE) and serotonin (5-HT) revealed that the fibers passing through the LH remained largely intact in the IBO treated rats. The results suggest that the observed aphagia and adipsia is not due to a lack of motivation, but rather reflects changes in the process which operate to initiate eating and drinking. Furthermore, selective neuronal degeneration induced the same behavioral changes as the electrolytic ones, though not to the same extent.     

5-hydroxytryptamine in the central nervous system and sexual receptivity of female rhesus monkeys.

The role of 5-hydroxytryptamine (5-HT) in the control of sexual receptivity in female rhesus monkeys has been studied in 24 adult females paired with 6 adult males. p-Chlorophenylalanine (PCPA, 75 mg/kg or 100 mg/kg, every fourth day), a selective inhibitor of 5-HT, was found to reverse unreceptivity induced by adrenalectomy in ovariectomised, oestrogen-treated females. PCPA-treated females presented more frequently and initiated more sexual behaviour, or else they refused fewer of the male's attempts to mount. These effects were in turn reversed by 5-hydroxytryptophan (5-HTP, 20 mg/kg every second day), when this was given to PCPA-treated animals. In addition, 5-HTP given alone to ovariectomised oestrogen-treated females reduced their receptivity. Parallel biochemical experiments showed that PCPA in the doses used lowered the levels of 5-HT in the brain as measured by the levels of 5-hydroxyindole-3-acetic acid (5-HIAA) in the CSF, and that these were restored by 5-HTP. Both oestradiol benzoate (15 mug/day for 10 days) and testosterone propionate (250 mug/day or 400 mug/day for 10 days) lowered the turn-over rates of 5-HT in the brain (as measured by the probenecid test) in ovariectomised female monkeys. These effects of oestradiol on turnover were antagonised by progesterone (15 mg/day for 10 days, given with oestradiol). A substance other than an adrenal androgen has thus been found to reverse the effects of adrenalectomy on sexual receptivity in female monkeys. It is therefore possible that androgens regulate receptivity in female monkeys by modifying the activity of 5-HT-containing neural systems.     

Hypothalamic involvement in the regulation of maternal behaviour in the rat: inhibitory roles for the ventromedial hypothalamus and the dorsal/anterior hypothalamic areas

The present report examines the possible involvement of the ventromedial hypothalamus (VMH), the dorsal hypothalamus (DH), and the anterior hypothalamic area (AHA) in the regulation of maternal behaviour in the female rat. In a series of experiments it was found that either infusions of saline or lowering cannulas into the VMH stimulated a rapid onset of maternal behaviour in progesterone plus oestrogen-primed, nulliparous rats. The stimulatory effect of cannula lowering into the VMH on maternal behaviour was shown to be steroid-dependent. Next, the involvement of cell bodies located in the DH/AHA in maternal behaviour was examined after bilateral lesions of these regions with the neurotoxin, N-methyl-D-aspartic acid (NMA). NMA lesions of the DH/AHA stimulated a rapid onset of maternal behaviour in oestrogen-treated, nulliparous rats, while NMA lesions in non-steroid-treated animals or vehicle infusions in steroid or non-steroid-treated rats failed to induce a rapid onset of behaviour. In a final study the effects of NMA lesions of the VMH were evaluated. As in AHA lesioned rats, NMA lesions of the VMH stimulated a fast onset of maternal behaviour in steroid-primed females. These findings indicate that the VMH as well as the DH/AHA exert chronic steroid-dependent inhibitory influences on the induction of maternal behaviour.     

The neurosteroids, progesterone and 3α,5α-THP, enhance sexual motivation, receptivity, and proceptivity in female rats

The effects of progesterone (P) and the neurosteroid and P metabolite, 3α-hydroxy-5α-pregnan-20-one (3α,5α-THP) on ovariectomized (ovx), estradiol-3-benzoate (EB)-primed rats on sexual motivation, receptivity, and proceptivity were examined. Changes in central P and 3α,5α-THP were measured following administration of EB, EB+P, EB+3α,5α-THP, or EB+inhibitor of 5α-reductase or P metabolism (epostane and finasteride)+P (Expt. 1). Partner preference was measured as the duration of time females in these different hormonal treatments spent in proximity to a male vs. female conspecific (Expt. 2). Receptivity (lordosis quotients and ratings) and proceptivity (darting, hopping, ear wiggling, and pacing), for different hormone treatments were assessed (Expt. 3 and Expt. 4, respectively). Conditioned place preference following hormone treatments and paced mating enabled assessment of sexual motivation (Expt. 5). Central P and 3α,5α-THP were measured in various combinations of hormone/mating conditions (Expt. 6). Studies revealed that 3α,5α-THP has a significant role in these reproductive measures. Brain concentrations of 3α,5α-THP were significantly higher in animals receiving EB+P or EB+3α,5α-THP compared to animals receiving EB alone, or EB+P in conjunction with an inhibitor of P metabolism. EB+P and EB+3α,5α-THP significantly increased time spent in proximity to the male, receptivity and proceptivity. When administered to ovx, EB-primed rats, the progestin metabolite, 3α,5α-THP, had effects on these behaviors similar to P. Epostane, an inhibitor of P and 3α,5α-THP biosynthesis, and finasteride, an inhibitor of P metabolism to 3α,5α-THP, administered to EB+P animals reduced male partner preference, proceptive, and receptive behaviors to levels seen in EB+vehicle animals. Notably, whole brain 3α,5α-THP levels were significantly increased and whole brain P levels were significantly reduced in paced mated rats compared to standard mated, and receptive non-mated animals. These studies suggest that P and 3α,5α-THP may have some common effects on reproductive behavior, e.g., sexual motivation, receptivity, and proceptivity.