Lordosis Behavior In Female Rats Research Articles

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.

Identification of neural cells activated by mating stimulus in the periaqueductal gray in female rats.

Induction of lordosis as typical female sexual behavior in rodents is dependent on a mount stimulus from males and blood levels of estrogen. Periaqueductal gray (PAG) efferent neurons have been suggested to be important for lordosis behavior; however, the neurochemical basis remains to be understood. In this study, we neuroanatomically examined (1) whether PAG neurons activated by mating stimulus project to the medullary reticular formation (MRF), which is also a required area for lordosis; and (2) whether these neurons are glutamatergic. Mating stimulus significantly increased the number of cFos-immunoreactive (ir) neurons in the PAG, particularly in its lateral region. Half of cFos-ir neurons in the lateral PAG were positive for a retrograde tracer (FluoroGold; FG) injected into the MRF. cFos-ir neurons also colocalized with mRNA of vesicular glutamate transporter 2 (vGLUT2), a molecular marker for glutamatergic neurons. Using retrograde tracing and in situ hybridization in conjunction with fluorescent microscopy, we also found FG and vGLUT2 mRNA double-positive neurons in the lateral PAG. These results suggest that glutamatergic neurons in the lateral PAG project to the MRF and are involved in lordosis behavior in female rats.

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.

A Selective Androgen Receptor Modulator Enhances Male-Directed Sexual Preference, Proceptive Behavior, and Lordosis Behavior in Sexually Experienced, But Not Sexually Naive, Female Rats

Androgens influence many aspects of reproductive behavior, including sexual preference of females for males. In oophorectomized women with sexual desire disorder, testosterone patches improve libido, but their use is limited because of adverse side effects. Selective androgen receptor modulators offer an improved safety profile for both sexes: enhancing libido and muscle and bone growth in a manner similar to steroidal androgens but with fewer adverse effects, such as hirsutism, acne, and prostate growth. The current study investigated the action of a novel selective androgen receptor modulator (LGD-3303 [9-chloro-2-ethyl-1-methyl-3-(2,2,2-trifluoroethyl)-3H-pyrrolo-[3,2-f]quinolin-7(6H)-one]) on male-directed sexual preference, proceptivity, and lordosis behavior of female rats. LGD-3303 is a nonsteroidal, nonaromatizable, highly selective ligand for the androgen receptor and effectively crosses the blood-brain barrier. Gonadectomized female rats were treated with LGD-3303 (3-30 mg/kg) or vehicle by daily oral gavage. Results showed that LGD-3303 treatment enhanced sexual preference of females for males but only if females had previous sexual experience. This occurred after 1 or 7 d of treatment. In contrast, preference for males was inhibited by LGD-3303 treatments of sexually naive females. The LGD-3303 increase in male preference was blocked by pretreatment with the androgen receptor antagonist flutamide. LGD-3303 treatment increased lordosis and proceptivity behaviors in ovariectomized females primed with suboptimal doses of estradiol benzoate plus progesterone. These data support the concept that LGD-3303 can stimulate aspects of female sexual behavior and may serve as a potential therapeutic for women with sexual desire disorders.

Influence of Neurotransmitters on Sexual Differentiation of Brain Structure and Function

Newborn rats received daily subcutaneous treatment with compounds which influence serotoninergic, cholinergic, alpha-adrenergic and beta-adrenergic activity. In adulthood luteinizing hormone (LH) secretion pattern, female sexual behavior, and the volume of the sexually dimorphic nucleus of the preoptic are (SDN-POA) were determined. Postnatal administration of l-tryptophan increased the volume of the SDN-POA significantly when given alone or when given simultaneously with testosterone propionate (TP). Para-chlorophenyl-alanine (pCPA) also increased SDN-POA volume, but did not potentiate the stimulating influence of TP. Clonidine had no effect per se on SDN-POA development, but it significantly potentiated the effect of TP in females. Salbutamol increased SDN-POA volume in females and in males. Postnatal treatment of female rats with the alpha-adrenergic receptor antagonists prazosine and yohimbine or with the nicotin receptor antagonist mecamylamine had permanent potentiating effects on the pattern of LH secretion, whereas postnatal treatment with beta-adrenergic compounds reduced the LH-release response to gonadal steroids in adulthood. Postnatal treatment with clonidin or l-tryptophane inhibited differentiation of the capacity for lordosis behavior. Beta-receptor agonists postnatally had a potentiating effect on the capacity for lordosis behavior in female and male rats. Cholinergic stimulation postnatally inhibited differentiation of the capacity for lordosis behavior in female rats, but prevented the inhibitory effect of postnatal androgenization. There was no correlation between SDN-POA volume and any of the two functional parameters.

Serotonin receptor involvement in effects of restraint on female rat lordosis behavior

Ovariectomized Fischer (CDF-344) rats, with bilateral cannulae in the mediobasal hypothalamus (MBH) near the ventromedial nucleus of the hypothalamus (VMN), were used to test the hypothesis that serotonin receptors in the VMN contribute to the lordosis-inhibiting effects of mild restraint. Rats were hormonally primed with 10 μg estradiol benzoate (EB) followed 48 h later with sesame seed oil. Four to six hours later (during the dark portion of the light–dark cycle), rats were pretested for sexual behavior. Thereafter, they were infused with saline, 2 μg of the serotonin (5-HT) 2 receptor agonist, (±)-2,5-dimethoxy-4-iodophenyl-2-aminopropane HCl (DOI), or 1 μg of the 5-HT 1A receptor antagonist, N-{2[4-(2-methoxyphenyl)-1-piperazinyl]ethyl}-N-(2-pyridinyl) cyclohexanecarboxamide trihydrochloride (WAY100635). After a 5 min restraint, rats were tested for sexual receptivity. Rats infused with saline showed a significant decline in lordosis behavior after restraint. Infusion with either DOI or WAY100635 attenuated these effects of restraint. These findings extend earlier observations that the lordosis-disruptive effects of mild restraint include activation of 5-HT 1A receptors in the VMN and are the first to implicate VMN 5-HT 2 receptors in protection against mild restraint.

The PKC inhibitor, bisindolymaleimide, blocks DOI's attenuation of the effects of 8-OH-DPAT on female rat lordosis behavior

Ovariectomized rats with bilateral cannulae near the ventromedial nucleus of the hypothalamus were hormonally primed with 10 μg estradiol benzoate and 500 μg progesterone. Sexually receptive females were infused bilaterally with 200 ng of the 5-HT 1A receptor agonist, 8-hydroxy-2-(di- n-propylamino) tetralin (8-OH-DPAT), or with a combination of 200 ng 8-OH-DPAT and 2000 ng of the 5-HT 2 receptor agonist, (±)-2,5-dimethoxy-4-iodophenyl-2-aminopropane HCl (DOI). 8-OH-DPAT inhibited lordosis behavior and DOI reduced this inhibition. However, if females were preinfused with the PKC inhibitor, bisindolymaleimide I hydrochloride (BIM), DOI's effect was eliminated. BIM's attenuation of the effects of DOI was time-dependent. When BIM was infused 90 min, but not 30 min, before the 5-HT receptor agonists, BIM eliminated DOI's protection against the lordosis-inhibiting effects of 8-OH-DPAT. A concentration of BIM as low as 10 −5 nmol in a 0.5 μl infusion volume was effective and there was little evidence of dose responsivity between 10 −5 and 10 −1 nmol of BIM. In contrast, prior infusion with vehicle or with 10 −7 nmol BIM had no impact on the female's response to the 5-HT receptor agonists. These findings allow the suggestion that DOI's ability to increase PKC may be responsible for attenuation of the effects of 8-OH-DPAT on lordosis behavior.

8-OH-DPAT attenuates isoproterenol- but not forskolin-stimulated accumulation of cAMP in mediobasal hypothalamus

Ovariectomized female rats were used to test the possibility that the 5-HT 1A receptor agonist, 8-hydroxy-2-(di- N-propylamino) tetralin (8-OH-DPAT), inhibits cyclic AMP (cAMP) accumulation in the mediobasal hypothalamus. Tissue slices were incubated with forskolin or with the β-adrenergic receptor agonist, isoproterenol, to stimulate accumulation of cAMP. Both compounds increased accumulation of cAMP. The 5-HT 1A receptor agonist, 8-OH-DPAT, reduced cAMP accumulation after stimulation by isoproterenol, but not after forskolin stimulation. These findings are discussed in terms of putative differences in the mechanisms whereby 5-HT 1A receptors are able to inhibit stimulation of adenylate cyclase. The potential significance of these findings to 5-HT 1A receptor-mediated inhibition of female rat lordosis behavior is also discussed.

Integration of steroid hormone initiated membrane action to genomic function in the brain

Estrogen is a ligand for the estrogen receptor (ER), which on binding 17β-estradiol, functions as a ligand-activated transcription factor and regulates the transcription of target genes. This is the slow genomic mode of action. However, rapid non-genomic actions of estrogen also exist at the cell membrane. Using a novel two-pulse paradigm in which the first pulse rapidly initiates non-genomic actions using a membrane-limited estrogen conjugate (E-BSA), while the second pulse promotes genomic transcription from a consensus estrogen response element (ERE), we have demonstrated that rapid actions of estrogen potentiate the slower transcriptional response from an ERE-reporter in neuroblastoma cells. Since rapid actions of estrogen activate kinases, we used selective inhibitors in the two-pulse paradigm to determine the intracellular signaling cascades important in such potentiation. Inhibition of protein kinase A (PKA), PKC, mitogen activated protein kinase (MAPK) or phosphatidylinositol 3-OH kinase (PI-3K) in the first pulse decreases potentiation of transcription. Also, our data with both dominant negative and constitutive mutants of Gα subunits show that Gα q initiates the rapid signaling cascade at the membrane in SK-N-BE(2)C neuroblastoma cells. We discuss two models of multiple kinase activation at the membrane Pulses of estrogen induce lordosis behavior in female rats. Infusion of E-BSA into the ventromedial hypothalamus followed by 17β-estradiol in the second pulse could induce lordosis behavior, demonstrating the applicability of this paradigm in vivo. A model where non-genomic actions of estrogen couple to genomic actions unites both aspects of hormone action.

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.

WAY100635 and female rat lordosis behavior

Sexually receptive proestrous rats with bilateral cannulae in the ventromedial nucleus of the hypothalamus (VMN) were infused with 200 ng of (±)-8-hydroxy-2-(di- n-propylamino) tetralin (8-OH-DPAT) or with 8-OH-DPAT plus varying concentrations (200 to 2000 ng) of the 5-HT 1A receptor antagonist, N-{2[4-(2-methoxyphenyl)-1-piperazinyl]ethyl}- N-(2-pyridinyl)cyclohexanecarboxamide trihydrochloride (WAY100635). 8-OH-DPAT inhibited lordosis behavior within 15 min of the infusion and every dose of WAY100635 prevented the inhibition. When non-sexually receptive, ovariectomized rats, hormonally primed with 0.5 μg estradiol benzoate and 500 μg progesterone, were infused with WAY100635 (400 to 2000 ng), the 5-HT 1A receptor antagonist did not facilitate lordosis responding. These findings support earlier findings that activation of 5-HT 1A receptors in the mediobasal hypothalamus inhibits lordosis behavior. However, they further demonstrate that tonic activation of 5-HT 1A receptors is not responsible for the absence of sexual receptivity in suboptimally hormonally primed ovariectomized rats.

Effect of estrogen on the lordosis-inhibiting action of ketanserin and SB 206553

The effects of the 5-HT 2A/2C receptor antagonist, ketanserin, and the 5-HT 2C receptor antagonist, SB 206553, on lordosis behavior were investigated in ovariectomized rats hormonally primed with estradiol benzoate (EB) (0.5 or 25 μg) and progesterone (500 μg). Both ketanserin and SB 206553 inhibited lordosis behavior after infusion into the ventromedial nucleus of the hypothalamus (VMN), but ketanserin was slightly more effective than the 5-HT 2C receptor antagonist. Either drug was more effective in rats primed with 0.5 μg EB than in rats hormonally primed with 25 μg EB. These findings support the suggestion that estrogen may enhance functioning of the 5-HT 2 receptor family and thereby protect against the 5-HT 2 receptor antagonists. These data are consistent with prior suggestions that estrogen modulates functioning of 5-HT 2 receptors within the VMN and that 5-HT 2 receptors play a facilitatory role in the modulation of female rat lordosis behavior.

Progesterone attenuates the effect of the 5-HT 1A receptor agonist, 8-OH-DPAT, and of mild restraint on lordosis behavior

Ovariectomized, hormone-primed rats were used to test the hypothesis that progesterone treatment attenuated the effects of the 5-HT 1A receptor agonist, (±)-8-hydroxy-2-(di- n-propylamino)tetralin (8-OH-DPAT), on female rat lordosis behavior. Based upon prior evidence that prepriming with estradiol benzoate (EB) reduced the ability of 8-OH-DPAT to inhibit lordosis behavior, rats were preprimed with 10 μg EB 7 days before a second priming with 10 μg EB followed 48 h later with 500 μg progesterone or vehicle. Independent of the presence of progesterone, prepriming with EB attenuated the lordosis-inhibiting effects of systemic treatment with 8-OH-DPAT. However, progesterone also reduced the effects of 8-OH-DPAT and this effect was also seen in females primed only once with EB. In contrast, progesterone was relatively ineffective in attenuating the effects of bilateral infusion with 8-OH-DPAT into the ventromedial nucleus of the hypothalamus (VMN). The failure of progesterone to substantially reduce the effects of VMN infusion with 8-OH-DPAT contrasts with prior studies in which estrogen’s protective action against the drug did include the VMN. Thus, while both estrogen and progesterone reduce the lordosis-inhibiting effect of 8-OH-DPAT, the mechanisms responsible for the effects of the two gonadal hormones may be different. Priming with progesterone also prevented the effects of 5 min of restraint. When rats were hormonally primed with EB and oil, rats showed a transient, but significant, decline in lordosis behavior 5 and 10 min after restraint. Rats primed with EB and progesterone were unaffected by the restraint. These results are discussed in terms of their implications for the role of progesterone in altering the 5-HT 1A receptor modulation of lordosis behavior.

Inhibition of lordosis behavior by intrahypothalamic infusion of a protein kinase G antagonist

Previous experiments demonstrated that intracerebroventricular infusion of the protein kinase G inhibitor KT5823 inhibits lordosis behavior in hormone-treated female rats. Present studies show that KT5823 attenuates lordosis in a dose-dependent manner when infused bilaterally into the ventromedial hypothalamus. Thus, activation of protein kinase G in the ventromedial hypothalamus is necessary for the expression of hormone-dependent lordosis behavior in female rats.

Estrogen modulates 5-HT 1A agonist inhibition of lordosis behavior but not binding of [ 3H]-8-OH-DPAT

Previous studies showed that repeated estrogen treatment reduces the ability of the 5-HT 1A receptor agonist, 8-hydroxy-2(di- n-propylamino) tetralin (8-OH-DPAT), to inhibit lordosis behavior of female rats. The present study evaluated the effects of repeated estrogen treatment on lordosis behavior and 5-HT 1A receptor binding and coupling to G protein in the hypothalamus-preoptic area using the agonist ligand [ 3H]-8-OH-DPAT, which binds selectively to G-protein-coupled 5-HT 1A receptors. Rats were injected twice with 25 or 50 μg of estradiol benzoate (EB) 7 days apart followed by 500 μg of progesterone (P) 48 h after the second EB injection. Controls received a single injection of 25 or 50 μg EB followed 48 h later by 500 μg of P. Four hours after P, 0.15 mg/kg 8-OH-DPAT was injected, and lordosis behavior examined for 30 min. Rats treated twice with EB showed significantly less 8-OH-DPAT inhibition of lordosis behavior than rats receiving a single EB injection. For receptor binding, rats received EB without P treatment. None of the estrogen treatments reduced [ 3H]-8-OH-DPAT binding density or affinity in the hypothalamus-preoptic area or hippocampus. These studies suggest that estrogen modulates 5-HT 1A agonist potency without a measurable change in 5-HT 1A receptor density or coupling to G protein.

The role of melanocortin receptors in sexual behavior in female rats

Earlier data have indicated that α-MSH may play a role for sexual behavior in rats. In this study we investigated the effects of MSH peptides on sexual receptivity in ovariectomized-adrenalectomized female rats, pre-treated with benzoate of estradiol, in presence of vigorous male rats. The results show that α-MSH significantly increases lordosis behavior in female rats after injections into the ventromedial nucleus. Interestingly, we have for the first time shown that γ-MSH also causes significant increase in lordosis in female rats. Furthermore, we show that HS014, an antagonist for the central MC receptors, in dose dependent manner blocks the effect of α-MSH on lordosis. The results indicate that the effects of MSH peptides on female sexual behaviour are mediated through a specific MC receptor, which could be the MC3 receptor.

Ovarian Hormone Dependence of α1-Adrenoceptor Activation of the Nitric Oxide–cGMP Pathway: Relevance for Hormonal Facilitation of Lordosis Behavior

The ovarian hormones estradiol (E(2)) and progesterone (P) facilitate rat lordosis behavior in part by regulating the expression of and signal transduction by adrenoceptors in the hypothalamus (HYP) and preoptic area (POA). The major adrenoceptor subtype mediating E(2) and P facilitation of lordosis is the alpha(1)-adrenoceptor. In the present studies, we tested the hypotheses that (1) alpha(1)-adrenoceptors in the HYP enhance lordosis responses by activating the nitric oxide (NO)-cGMP signaling pathway, and (2) coupling of alpha(1)-adrenoceptors to this signal transduction pathway is hormone-dependent. Basal levels of cGMP were significantly higher in HYP and POA slices from animals treated with E(2) and P when compared with slices from ovariectomized controls or females treated with only E(2) or P. When slices of HYP and POA from ovariectomized female rats were incubated with norepinephrine or the selective alpha(1)-adrenoceptor agonist phenylephrine, cGMP accumulation was observed only if slices had been derived from females treated with both E(2) and P before experimentation. Moreover, alpha(1)-adrenoceptor stimulation of cGMP synthesis was blocked by an inhibitor of NO synthase, confirming that these receptors act by NO-mediated stimulation of soluble guanylyl cyclase. Behavioral studies demonstrated further that the cell-permeable cGMP analog 8-bromoadenosine-cGMP reverses the inhibitory effects of the alpha(1)-adrenoceptor antagonist prazosin on lordosis behavior in E(2)- and P-treated female rats. Thus, the NO-cGMP pathway mediates the facilitatory effects of alpha(1)-adrenoceptors on lordosis behavior in female rats, and previous exposure of the HYP and POA to both E(2) and P are required to link alpha(1)-adrenoceptors to this pathway.

Effects of Prenatal Morphine Exposure on Rat Heterotypical Sexual Behavior

Prenatal exposure to morphine inhibits ovarian steroid-dependent lordosis behavior in female rats, and enhances certain components of male sexual behavior in male rats. In the present study, the effects of mid to late gestational morphine exposure on male sexual behavior in females and on female sexual behavior in males were examined in adult offspring. Gonadectomized male rats were injected at weekly intervals with 30 or 60 μg estradiol benzoate and 1.0 mg progesterone and tested for female sexual behavior with stimulus males on 2 consecutive weekly tests. Ovariohysterectomized (OVX) females were injected with 500 μg testosterone propionate (TP) daily for 15 days and tested for male sexual behavior with stimulus females on the last day of TP injection and 1 week later, after TP withdrawal. Prenatal morphine exposure increased the expression of male sexual behaviors in female rats, but it did not increase lordosis behavior in male rats. Thus, exposure to morphine during gestation alters male and female sexual behavior in young adult animals. Because prenatal morphine exposure both defeminized and masculinized adult sexual behavior in female rats, it is possible that female brain development is more vulnerable to prenatal insult such as opiate exposure.

5-HT 2C receptor involvement in female rat lordosis behavior

Adult, hormone-primed, ovariectomized rats (CDF-344) with bilateral implants within the ventromedial nucleus of the hypothalamus (VMN), were injected with 0.5 μg estradiol benzoate followed 48 h later with 500 μg progesterone. This priming produced rats with 2 different levels of sexual receptivity. Rats with a lordosis to mount ratio (L/M)≥0.5 were used to examine the potential lordosis-inhibiting effects of the 5-HT 2A receptor antagonist, R(+)-a-(2,3-dimethoxyphenyl)-1-[2(4-fluoro-phenylethyl)]-4-piperidine-methanol (MDL 100,907), and the 5-HT 2C receptor antagonist, 5-methyl-1-(3-pyridylcarbamoyl)-1,2,3,5-tetrahydropyrrolo[2,3- f]indole (SB 206553). Rats with low sexual receptivity (L/M<0.5) were bilaterally infused with the 5-HT 2A/2C receptor agonist, (±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl (DOI), or DOI plus either MDL 100,907 or SB 206553 to determine if either drug would attenuate the lordosis-facilitating effects of DOI. The 5-HT 2C receptor antagonist, but not the 5-HT 2A receptor antagonist, effectively inhibited lordosis behavior. Similarly, SB 206553 was more effective than MDL 100,907 in reducing the DOI-induced increase in lordosis responding. However, both drugs limited the duration of lordosis responding initiated by DOI. These results are consistent with prior suggestions that 5-HT 2A/2C receptors within the VMN are involved in the modulation of lordosis behavior and lead to the suggestion that 5-HT 2C, rather than 5-HT 2A, receptors are primarily responsible for the effects of 5-HT 2 receptor-active drugs on lordosis behavior.

Functional integration among 5-hydroxytryptamine receptor families in the control of female rat sexual behavior

Serotonin (5-HT) receptor interaction in the control of female rat lordosis behavior was examined. Ovariectomized rats, with bilateral implants in the ventromedial nucleus of the hypothalamus (VMN), were hormonally primed with 25 μg estradiol benzoate and 500 μg progesterone. Rats were infused with the 5-HT 3 receptor antagonist, 3-tropanyl-indole-3 carbonylate (tropisetron; 500 ng), or were coinfused with the 5-HT 3 receptor antagonist and the 5-HT 2A/2C receptor agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI; 500, 1500, or 2000 ng). Additional ovariectomized, hormone-primed rats received bilateral VMN infusions with the 5-HT 1A receptor agonist, 8-hydroxy-2-(di- n-propylamino) tetralin (8-OH-DPAT; 200 ng), or were coinfused with the 5-HT 1A receptor agonist and the 5-HT 3 receptor agonist, m-chlorophenyl-biguanide (mCPBG; 250, 500, or 1000 ng). Lordosis behavior was observed prior to VMN infusion, during the infusion and for 30 consecutive minutes thereafter. Tropisetron reduced the lordosis to mount (L/M) ratio in every animal investigated but the decline was attenuated by coinfusion with DOI. Similarly, the L/M ratio declined following infusion with 8-OH-DPAT and the decline was dose-dependently reduced by coinfusion with mCPBG. Only the 5-HT 3 receptor agonist altered the quality of the lordosis reflex. These studies provide evidence that the effects of 5-HT on female rat lordosis behavior involve the integrated activity of at least 3 different 5-HT receptor families.