Facilitation Of Lordosis Behavior Research Articles

Participation of kisspeptin, progesterone, and GnRH receptors on lordosis behavior induced by kisspeptin

The neuropeptide kisspeptin (Kiss) is crucial in regulating the hypothalamic-pituitary-gonadal axis. It is produced by two main groups of neurons in the hypothalamus: the rostral periventricular region around the third ventricle and the arcuate nucleus. Kiss is the peptide product of the KiSS-1 gene and serves as the endogenous agonist for the GPR54 receptor. The Kiss/GPR54 system functions as a critical regulator of the reproductive system. Thus, we examined the effect of intracerebroventricular administration of 3 μg of Kiss to the right lateral ventricle of ovariectomized rats primed with a dose of 5 μg subcutaneous (sc) of estradiol benzoate (EB). Kiss treatment increased the lordosis quotient at all times tested. However, the lordosis reflex score was comparatively lower yet still significant compared to the control group. To investigate receptor specificity and downstream mechanisms on lordosis, we infused 10 μg of GPR54 receptor antagonist, Kiss-234, 5 μg of the progestin receptor antagonist, RU486, or 3 μg of antide, a gonadotropin-releasing hormone-1 (GnRH-1) receptor antagonist, to the right lateral ventricle 30 min before an infusion of 3 μg of Kiss. Results demonstrated a significant reduction in the facilitation of lordosis behavior by Kiss at 60 and 120 min when Kiss-234, RU486, or antide were administered. These findings suggest that Kiss stimulates lordosis expression by activating GPR54 receptors on GnRH neurons and that Kiss/GPR54 system is an essential intermediary by which progesterone activates GnRH.

Participation of the nitric oxide pathway in lordosis induced by apelin-13 in female rats

The present study investigated the participation of the nitric oxide pathway in facilitating lordosis behavior induced by intrahypothalamic administration of apelin-13 in ovariectomized rats primed with estradiol benzoate (EB). The experiments involved the administration of a nitric oxide synthase inhibitor (L-NAME) or a nitric oxide-dependent, soluble guanylyl cyclase inhibitor (ODQ), and an inhibitor of protein kinase G (KT5823) to the ventromedial hypothalamus (VMH) of EB-primed rats 30 min before infusion of apelin-13 (0.75 μg/μl). This dose of apelin-13 consistently induces lordosis behavior at 30 min, 120 min, and 240 min following infusion. Results showed that injections of either L-NAME or KT5823 significantly reduced the lordosis induced by apelin at 120 and 240 min. However, VMH infusion of ODQ 30 min before apelin-13 infusion reduced but did not significantly inhibit, the lordosis elicited by this peptide at the same time points. We conclude that the nitric oxide pathway in the VMH plays an important role in lordosis induced by apelin-13 in EB-primed rats.

Oxytocin induces lordosis behavior in female rats through the prostaglandin E2/GnRH signaling system

Intracerebroventricular (icv) administration of oxytocin (OT) induces robust lordosis behavior (lordosis quotient and lordosis intensity) in estrogen-primed rats. The present study explored the hypothesis that the OT-Prostaglandin E2-GnRH pathway (a pathway produced in astrocytes) is involved in the facilitation of lordosis behavior by icv infusion of OT (2 μg). In Experiment 1, we tested the involvement of the OT receptor (OTR) by infusion of the OTR antagonist, atosiban (ATO). OT-induced lordosis was significantly reduced at both 30 and 120 min by prior infusion of ATO. In Experiment 2, we studied the effects of aspirin (COX2 inhibitor) and ONO-AE3-208 (ONO; EP4 prostaglandin receptor antagonist) on OT-induced lordosis. Infusions of both compounds diminished OT-induced lordosis at both 120 and 240 min. In Experiment 3, the involvement of the GnRH-1 receptor inhibitor antide on OT-induced lordosis was evaluated. Antide significantly inhibited OT-induced lordosis at all times tested. These data indicate that the OT/PGE2/GnRH pathway is involved in the expression of OT-induced lordosis behavior, an effect that may be occurring directly in hypothalamic astrocytes.

Analyses of rapid estrogen actions on rat ventromedial hypothalamic neurons

Rapid estrogen actions are widely diverse across many cell types. We conducted a series of electrophysiological studies on single rat hypothalamic neurons and found that estradiol (E2) could rapidly and independently potentiate neuronal excitation/depolarizations induced by histamine (HA) and N-Methyl-d-Aspartate (NMDA). Now, the present whole-cell patch study was designed to determine whether E2 potentiates HA and NMDA depolarizations – mediated by distinctly different types of receptors – by the same or by different mechanisms. For this, the actions of HA, NMDA, as well as E2, were investigated first using various ion channel blockers and then by analyzing and comparing their channel activating characteristics. Results indicate that: first, both HA and NMDA depolarize neurons by inhibiting K+ currents. Second, E2 potentiates both HA and NMDA depolarizations by enhancing the inhibition of K+ currents, an inhibition caused by the two transmitters. Third, E2 employs the very same mechanism, the enhancement of K+ current inhibition, thus to rapidly potentiate HA and NMDA depolarizations. These data are of behavioral importance, since the rapid E2 potentiation of depolarization synergizes with nuclear genomic actions of E2 to facilitate lordosis behavior, the primary female-typical reproductive behavior.

Estrogen receptors regulate the estrous behavior induced by progestins, peptides, and prostaglandin E2

The role of classical estrogen receptors (ERs) in priming female reproductive behavior has been studied previously; however, the participation of this receptor during activation of estrous behavior has not been extensively studied. The purpose of this work was to test the possibility that the facilitation of lordosis behavior in estrogen-primed rats by progesterone (P) and its 5α- and 5β-reduced metabolites, gonadotropin-releasing hormone (GnRH), leptin, prostaglandin E2 (PGE2) and vagino-cervical stimulation (VCS) involves interactions with classical ERs by using the selective ER modulator, tamoxifen. To further assess the role of ERs, we also explored the effects of the pure ER antagonist, ICI182780 (ICI), on estrous behavior induced by P and GnRH. Ovariectomized, estrogen-primed rats (5μg estradiol benzoate 40h earlier) were injected intraventricularly with the above-mentioned compounds, or they received VCS. All compounds and VCS effectively facilitated estrous behavior when tested at 60, 120 or 240min after infusion or application of VCS. Intraventricular infusion of tamoxifen (5μg), 30min before, significantly attenuated estrous behaviors induced in estradiol-primed rats by P, most of its 5α- and 5β-reduced metabolites, GnRH, and PGE2, but not by VCS. Although there was a trend for reduction, tamoxifen did not significantly decrease lordosis in females treated with 5β-pregnan-3,20-dione. ICI also inhibited lordosis behavior induced by P and GnRH at some testing intervals. These results suggest that activation of classical ERs participates in the triggering effects on estrous behavior induced by agents with different chemical structures that do not bind directly to ERs.

The nitric oxide pathway participates in lordosis behavior induced by central administration of leptin

Intracerebroventricular (icv) administration of leptin facilitates lordosis behavior in ad libitum-fed, estrogen-primed rats. The cellular mechanism involved in this response is unknown. The present study tested the hypothesis that the nitric oxide-guanylyl cyclase, cGMP-dependent protein kinase (PKG) pathway is involved in the facilitation of lordosis behavior induced by the central administration of leptin. We tested the importance of the nitric oxide/cGMP pathway for lordosis stimulation by either icv infusion of a nitric oxide synthase inhibitor (L-NAME) or a nitric oxide-dependent, soluble guanylyl cyclase inhibitor (ODQ) 30 min before leptin administration (1 μg). This dose of leptin reliably induced lordosis behavior in ovariectomized estradiol benzoate treated rats. The lordosis induced by leptin at 1 and 2h after infusion was significantly reduced by the previous injection of either L-NAME or by ODQ. Intracerebroventricular infusion of the PKG inhibitor (KT5823) 30 min before leptin infusion, also significantly inhibited the lordosis behavior induced by leptin at 1 and 2h after hormone administration. These data support the hypothesis that the nitric oxide/cGMP/PKG pathway is involved in the facilitation of lordosis by leptin in estrogen-primed female rats.

Leptin facilitates lordosis behavior through GnRH-1 and progestin receptors in estrogen-primed rats

Dose response curves for leptin facilitation of estrous behavior (lordosis and proceptivity) were made by infusing the peptide into the lateral ventricle (icv) of ovariectomized (ovx), ad libitum-fed rats injected 40h previously with 5μg of estradiol benzoate. Leptin doses of 1 and 3μg produced significant lordosis quotient at 60min post-injection, with maximal lordosis being displayed at 120min. Yet the intensity of lordosis was weak, and a high incidence of rejection behaviors was found. Moreover, leptin did not induce significant proceptive behaviors at any dose. The leptin doses of 1 and 3μg were selected for determining whether antide, a GnRH-1 receptor antagonist, or the progestin receptor antagonist RU486 could modify the lordosis response to leptin. Icv injection of either antide or RU486 1h before leptin significantly depressed leptin facilitation of lordosis. The results suggest that leptin stimulates lordosis by releasing GnRH, which in turn activates GnRH-1 and progestin receptors. The physiological role of leptin in the control of estrous behavior remains to be determined.

Estradiol modulation of phenylephrine-induced excitatory responses in ventromedial hypothalamic neurons of female rats

Estrogens act within the ventromedial nucleus of the hypothalamus (VMN) to facilitate lordosis behavior. Estradiol treatment in vivo induces alpha(1b)-adrenoreceptor mRNA and increases the density of alpha(1B)-adrenoreceptor binding in the hypothalamus. Activation of hypothalamic alpha(1)-adrenoceptors also facilitates estrogen-dependent lordosis. To investigate the cellular mechanisms of adrenergic effects on VMN neurons, whole-cell patch-clamp recordings were carried out on hypothalamic slices from control and estradiol-treated female rats. In control slices, bath application of the alpha(1)-agonist phenylephrine (PHE; 10 microM) depolarized 10 of 25 neurons (40%), hyperpolarized three neurons (12%), and had no effect on 12 neurons (48%). The depolarization was associated with decreased membrane conductance, and this current had a reversal potential close to the K(+) equilibrium potential. The alpha(1b)-receptor antagonist chloroethylclonidine (10 microM) blocked the depolarization produced by PHE in all cells. From estradiol-treated rats, significantly more neurons in slices depolarized (71%) and fewer neurons showed no response (17%) to PHE. PHE-induced depolarizations were significantly attenuated with 4-aminopyridine (5 mM) but unaffected by tetraethylammonium chloride (20 mM) or blockers of Na(+) and Ca(2+) channels. These data indicate that alpha(1)-adrenoceptors depolarize VMN neurons by reducing membrane conductance for K(+). Estradiol amplifies alpha(1b)-adrenergic signaling by increasing the proportion of VMN neurons that respond to stimulation of alpha(1b)-adrenergic receptors, which is expected in turn to promote lordosis.

Hormone Effects on Specific and Global Brain Functions

The first demonstration of how biochemical changes in neurons in specific parts of the brain direct a complete mammalian behavior derived from the effects of estrogens in hypothalamic neurons that facilitate lordosis behavior, the primary reproductive behavior of female quadrupeds (Pfaff. Estrogens and Brain Function. 1980; Pfaff. Drive: Neurobiological and Molecular Mechanisms of Sexual Motivation. 1999). Sex behaviors depend on sexual arousal that in turn depends on a primitive function: generalized CNS arousal (Pfaff. Brain Arousal and Information Theory. 2006). Here we summarize one of the ways in which a generalized arousal transmitter, norepinephrine, can influence the electrical excitability of ventromedial hypothalamic cells in a way that will foster female sex behavior.

The role of progestin receptors and the mitogen-activated protein kinase pathway in δ opioid receptor facilitation of female reproductive behaviors

The present study investigated the role of the progestin receptor (PR) and the mitogen-activated protein kinase (MAPK) pathway in the facilitation of lordosis behavior by the δ opioid receptor agonist [ d-Pen 2, d-Pen 5]-enkephalin (DPDPE). Ovariectomized, estrogen-primed rats were treated with the PR antagonist RU486 or the MAPK inhibitor PD98059 prior to intraventricular (icv) infusion of DPDPE. Both RU486 and PD98059 blocked receptive and proceptive behaviors induced by DPDPE at 60 min, and RU486 continued to inhibit estrous behavior at 90 min. Because δ opioid receptors can activate the p42/44 MAPKs, extracellular signal regulated kinases (ERK), we determined the effects of DPDPE on ERK phosphorylation. Icv infusion of DPDPE increased the levels of phosphorylated ERK in the hypothalamus and preoptic area of female rats, assessed by immunoblotting. These results support the participation of the PR and the MAPK pathway in the facilitation of lordosis behavior by δ opioid receptors.

GABA A-5-HT 1A receptor interaction in the mediobasal hypothalamus

Both serotonin (5-HT) and γ-aminobutyric acid (GABA) modulate female rat lordosis behavior and appear to interact in their control of the behavior. The current experiments were designed to investigate the interaction between these two neurotransmitters in sexually receptive female rats. Ovariectomized female rats, with bilateral cannulae directed toward the ventromedial nucleus of the hypothalamus (VMN), were hormonally primed with 10 μg estradiol benzoate and 500 μg progesterone. Sexual behavior was examined after intracranial infusion with 200 ng (±)-8-hydroxy 2-(di- n-propylamino)tetralin (8-OH-DPAT), 25 ng (5-aminomethyl-3-hydroxyisoxazole)hydrobromide (muscimol), 10 ng bicuculline or a combination of the drugs. As expected, 8-OH-DPAT reduced lordosis behavior and muscimol attenuated this inhibition in a bicuculline-sensitive manner. Muscimol alone also reduced lordosis behavior. These findings contrast with several reports that muscimol facilitates lordosis behavior of suboptimally hormonally primed female rats. The current outcome is discussed in terms of procedural differences between the present experiment and earlier studies. It is suggested that muscimol may enhance lordosis responding in suboptimally hormonally primed rats by activation of GABA A receptors located dorsal to the VMN. In contrast, activation of receptors located more ventrally within the mediobasal hypothalamus (MBH) may inhibit the behavior of rats that are already sexually receptive.

Regulation of lordosis by cyclic 3',5'-guanosine monophosphate, progesterone, and its 5alpha-reduced metabolites involves mitogen-activated protein kinase.

Progesterone (P) and its ring A-reduced metabolites regulate sexual behavior in ovariectomized, estrogen-primed female rats when they are administered intracerebrally and systemically. The present study tested the hypothesis that the MAPK pathway participates in P facilitation and sequential inhibition of sexual behavior. The role of MAPK in lordosis facilitation by two ring A-reduced metabolites of P, 5alpha-dihydroprogesterone (5alpha-DHP) and 5alpha,3alpha-pregnanolone (5alpha,3alpha-Pgl), was also assessed. In Experiment 1, the MAPK inhibitor PD98059 was infused intracerebroventricularly before progestin administration. Lordosis behavior induced by P, 5alpha-DHP, and 5alpha,3alpha-Pgl was abolished 2 h after progestin administration by PD98059. P and 5alpha,3alpha-Pgl facilitation of proceptive behaviors was also decreased by the MAPK inhibitor. Experiment 2 examined the effects of MAPK inhibition on P sequential inhibition. Estrogen-primed females received intracerebroventricular infusions of PD98059 or vehicle 30 min before systemic administration of P and were tested for lordosis 4 h later. Animals received a second injection of P 24 h later and were retested for lordosis. The MAPK inhibitor blocked both lordosis facilitation and sequential inhibition produced by systemic administration of P. Because cGMP can also facilitate lordosis behavior, and cGMP-dependent protein kinase can activate MAPK, experiment 3 determined whether interference with MAPK would affect cGMP enhancement of lordosis. The icv infusion of PD98059 significantly inhibited lordosis behavior induced by 8-bromo-cGMP, a cell-permeable cGMP analog, at both 2 and 4 h. These data support the hypothesis that the MAPK pathway is involved in lordosis regulation by P and some of its ring A-reduced metabolites as well as by the second messenger, cGMP.

Estrogen and progesterone dose-dependently reduce disruptive effects of restraint on lordosis behavior

Ovariectomized rats were hormonally primed with various doses of estradiol benzoate (EB; 0.5–10 μg) in combination with various doses of progesterone (2.5–500 μg) to induce sexual receptivity. Females were then subjected to 5 min restraint and the effect on lordosis behavior was monitored for the next 30 min. Such mild stress has been previously shown to transiently reduce lordosis behavior of ovariectomized females hormonally primed only with 10 μg EB. In the current study, doses of progesterone of 25 μg or more in combination with 10 μg EB reduced the effects of restraint. Also priming doses of EB from 4.0 to 10 μg in combination with 250 μg progesterone prevented the lordosis-inhibiting effects of restraint. These findings reinforce prior observations of the dose-dependency of both estrogen and progesterone in the facilitation of lordosis behavior and introduce the female's lordosis response to mild restraint as a potentially useful index of the female's response to stress.

Ovarian steroid and growth factor regulation of female reproductive function involves modification of hypothalamic alpha 1-adrenoceptor signaling.

The ovarian steroids estradiol (E(2)) and progesterone (P) act on target neurons in the hypothalamus and preoptic area to coordinate the expression of female reproductive behaviors with the timing of the preovulatory luteinizing hormone (LH) surge. This chapter will summarize evidence that E(2) and P facilitation of the receptive component of female reproductive behavior, lordosis, involves changes in both the expression of and intracellular signal transduction pathways engaged by alpha(1)-adrenergic receptors in the hypothalamus and preoptic area. The alpha(1)-adrenoceptors are thought to mediate the facilitatory effects of the catecholamine neurotransmitter norepinephrine on both lordosis behavior and LH release. E(2) first induces the expression of the alpha(1B)-adrenergic receptor subtype in the hypothalamus and preoptic area. P then acts in an E(2)-dependent manner to promote linkage of hypothalamic alpha(1)-adrenoceptors to an intracellular signaling pathway involving nitric oxide and cyclic GMP. This chapter will also describe recent findings that implicate brain insulin-like growth factor-I (IGF-I) receptors as obligatory co-mediators of hormonal regulation of hypothalamic alpha(1)-adrenoceptors and female neuroendocrine function. Additional studies suggest that E(2) and IGF-I facilitate lordosis behavior by activating kinases traditionally associated with growth factor signal transduction (mitogen-activated protein kinases and phosphatidlyinositol-3-kinases). These molecular events are proposed to help coordinate the timing of ovulation with the expression of sexual receptivity, thereby maximizing reproductive success.

The role of δ-opioid receptors in estrogen facilitation of lordosis behavior

The present study investigated the role of δ-opioid receptors (ORs) in estrogen facilitation of female rat reproductive behavior (lordosis). Infusion of 2 μg of the selective δ-OR agonist [D-Pen 2,D-Pen 5]-enkephalin (DPDPE), into the third ventricle facilitated lordosis behavior in ovariectomized (OVX) rats injected with estrogen (E) 48 and 24 h before behavioral testing. Pretreatment with the selective δ-OR antagonist naltrindole (NTDL) blocked DPDPE effects on lordosis behavior. Ventricular infusion of NTDL (40 μg) also suppressed lordosis behavior in fully receptive OVX rats primed with both E and progesterone (P). In addition, NTDL blocked lordosis behavior when infused into the ventromedial nucleus of the hypothalamus (VMH) but not into the medial preoptic area (mPOA). Site-specific infusion of DPDPE into the VMH had dose-dependent, dual effects on lordosis behavior. While a very low dose of DPDPE (0.01 μg) facilitated lordosis behavior, a higher dose (1.0 μg) inhibited receptivity in OVX rats primed with E and a low dose (50 μg) of P. We used 3H-DPDPE to measure the density of δ-ORs in OVX rats treated with vehicle or with E by receptor autoradiography. E treatment did not have any effect on the density of DPDPE binding sites in the VMH, mPOA, medial amygdala, or caudate putamen. The behavioral effects of the ligands used in this study suggest that activation of δ-OR in the VMH by endogenous opioids facilitates estrogen-dependent lordosis behavior.

Castration rapidly decreases hypothalamic γ-aminobutyric acidergic neuronal activity in both male and female rats

The postcastration LH response is greater and somewhat more rapid in male than female rats. We have previously demonstrated that hypothalamic γ-aminobutyric acid (GABA)ergic neuronal activity decreases following gonadectomy in male rats. To investigate whether these same hypothalamic GABA neurons decrease their activity postcastration in female rats, and whether more rapid and or greater postcastration decreases occur in male rats, we determined the timing and magnitude of the postcastration decreases in GABA turnover which are associated with the sexually dimorphic postcastration LH response. Adult male and 4-day cycling female rats were castrated between 0800 and 1000 h (females ovariectomized on diestrus day 1). Serum LH levels increased significantly by 12 h postcastration in both males and females with the magnitude of the increases being 6.2-fold in males and 2.8-fold in females. GABA turnover was determined in 16 microdissected brain structures by the GABA transaminase inhibition method at 0 h (sham-operated controls), 6 h, 12 h and 1, 2, 4 and 6 days postcastration. In male rats, in the diagonal band of Broca at the level of the organum vasculosum of the lamina terminalis [DBB(ovlt)], the rate of GABA turnover decreased significantly already by 6 h postcastration compared with the 0 h controls, and remained suppressed through 6 days. This rapid down regulation of DBB(ovlt) GABAergic neurons also occurred in female rats, however, the duration of the decrease was not as prolonged as in male rats. Similar changes occurred in the tuberoinfundibular GABAergic (TIGA) neurons projecting to the median eminence in both males and females. Down regulation of these GABAergic neurons precedes or is coincident with increased postcastration LH secretion in both sexes, and the duration of the decreases is consistent with the less robust postcastration LH response in female rats. In addition, the rate of GABA turnover decreased after castration in the interstitial (bed) nucleus of the stria terminalis, ventral aspect (INSTv), the medial preoptic nucleus, dorsomedial aspect (MPNdm) and the ventromedial nucleus, ventrolateral aspect (VMNvl) in male rats, and in the INSTv and VMNvl of female rats, while there was no effect of castration in other hypothalamic regions or control structures. The result in the female VMNvl is consistent with reports that GABA facilitates lordosis behavior in this hypothalamic structure. These findings are consistent with the hypothesis that discrete hypothalamic populations of sex steroid-sensitive GABAergic neurons mediate the postcastration LH responses in both male and female rats, and may underlie other sexually dimorphic adult phenotypes such as sex behavior.

Attenuation of the lordosis-inhibiting effects of 8-OH-DPAT by TFMPP and quipazine

Regularly cycling, proestrous female rats received infusions of 200 ng of the serotonin (5-HT) 1A receptor agonist, (±) 8-hydroxy 2-(di- n-propylamino) tetralin-HBr (8-OH-DPAT), or 200 ng 8-OH-DPAT and 1000 or 2000 ng of N-(3-trifluoro-methylphenyl) piperazine hydrochloride (TFMPP) or 2-(1-piperazinyl) quinoline dimaleate (quipazine). Infusions were made bilaterally into the ventromedial nucleus of the hypothalamus (VMN). Animals receiving 200 ng 8-OH-DPAT exhibited a decline in lordosis behavior following infusion. Rats receiving 8-OH-DPAT and 1000 or 2000 ng quipazine or TFMPP were protected from the lordosis-inhibiting effects of 8-OH-DPAT, alone. Although both quipazine and TFMPP act on multiple 5-HT receptors, they overlap in their agonist action at 5-HT 2 receptors. Consequently, these results provide further evidence supporting the contention that within the VMN, both 5-HT 1A and 5-HT 2 receptor subtypes contribute to the modulation of lordosis behavior in the female rat. The data are discussed in terms of the relative potency of 5-HT at 5-HT receptors mediating inhibition and facilitation of lordosis behavior.

Facilitation of female rat lordosis behavior by hypothalamic infusion of 5-HT 2A/2C receptor agonists

Ovariectomized rats were hormonally primed with 0.5 μg estradiol benzoate and 500 μg progesterone to produce two groups of rats differing in their lordosis behavior. Females with a lordosis to mount (L/M) ratio <0.5 were used to test the hypothesis that 5-HT 2A/2C receptor agonists could facilitate lordosis behavior. Females with L/M ratios ≥0.5 were used to evaluate the potential suppressive effect of 5-HT 2A/2C receptor compounds. Lordosis behavior was examined following bilateral infusion of drugs into the ventromedial nucleus of the hypothalamus (VMN). Drugs examined were the 5-HT 2A/2C receptor agonist, (±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl (DOI), the 5-HT 2A/2C receptor antagonist, 3-[2-[4-(4-fluorobenzoyl)-1-piperdinyl]ethyl]-2,4(1 H,3 H)-quinazolinedione tartrate (ketanserin tartrate), and the non-selective 5-HT receptor agents, 2-(1-piperazinyl)quinoline dimaleate (quipazine) and N-(3-trifluoromethylphenyl)piperazine HCl (TFMPP). Drugs with agonist action at 5-HT 2A/2C receptors increased lordosis behavior in rats with low sexual receptivity. The 5-HT 2A/2C receptor antagonist, ketanserin, inhibited lordosis behavior in sexually receptive rats. DOI attenuated the lordosis-inhibiting effect of ketanserin, but ketanserin was less effective in preventing DOI from increasing lordosis behavior. These results strengthen prior inferences that activation of 5-HT 2A/2C receptors can facilitate lordosis behavior and that the VMN is one site at which such facilitation can occur.

Orphanin FQ/nociceptin in the ventromedial nucleus facilitates lordosis in female rats.

The localization of opioid receptor-like (ORL-1) orphan receptor in the ventromedial nucleus of the hypothalamus (VMH) suggested a role for this opioid system in the regulation of lordosis behavior. Recently, the ligand for ORL-1, orphanin FQ/nociceptin (OFQ/N), has been characterized and also demonstrated to be present in the VMH. The present experiments examined whether OFQ/N in the VMH facilitates lordosis behavior in estrogen-primed, sexually unreceptive female rats, and whether estrogen regulates ORL-1 levels in the VMH. Estrogen was shown to increase ORL-1 immunoreactivity in the VMH, and microinfusions of OFQ/N into the VMH facilitated lordosis behavior in a dose-dependent manner.

Effects of neuropeptide Y (NPY) and NPY agonists on lordosis in the female guinea pig

We have previously shown that an NPY antagonist decreases lordosis behavior and that this decrease can be reversed with NPY administration. The present experiments examined whether intracerebroventricular (icv) administration of NPY would facilitate lordosis behavior and whether it would increase feeding behavior in the female guinea pig. Additionally, we examined whether icv administration of a more specific NPY Y1 and/or Y2 receptor agonist would facilitate lordosis behavior. Although NPY (1 μg) increased feeding behavior when it was administered to the lateral ventricle of ovariectomized (ovx) estrogen (i.e., estradiol benzoate; EB) and progesterone- (P) treated guinea pigs, it had no facilitatory effect on lordosis behavior at any of the doses tested (0.5, 1, 5, or 10μg). In fact, the lower doses had a small, delayed inhibitory effect. NPY also had no effect on lordosis in females treated with EB alone. In contrast, the NPY Y1 agonist (Leu(31)Pro(34)) NPY significantly facilitated lordosis in ovx EB- and P-treated females. It had no effect in ovx females treated with EB alone. The NPY Y2 agonist NPY (13-36) had a slight, delayed inhibitory effect in ovx EB- and P-treated females. These data are consistent with the hypothesis that NPY can act at a number of receptor subtypes to affect lordosis behavior, and that NPY can facilitate lordosis behavior by acting at Y1 receptors. Furthermore, it appears that this facilitatory effect of Y1 receptors is an effect on some progesterone-mediated component of lordosis, as the Y1 agonist facilitated EB- and P-induced lordosis, but not that induced with EB alone.