Habenular lesions and feminine sexual behavior of ovariectomized rats: Diminished responsiveness to the synergistic effects of estrogen and progesterone.

Modianos, Doan T.; Hitt, John C.; Popolow, Herbert B.

doi:10.1037/h0076805

Cited by 50 publications

(20 citation statements)

References 17 publications

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“…In addition, the observation that exposure of the midbrain Hab region to RU 38486 reduced lordosis behavior in 5 of 14 rats tested leaves open the possibility that the Hab or other midbrain sites may be important secondary targets of P facilitation of estrous behavior as well. Indeed two laboratories have reported that lesions 1616 RU 38486, ESTROUS BEHAVIOR, AND BRAIN P RECEPTORS Endo • 1986 Volll9«No4 of the Hab decrease both receptivity and proceptivity in estrogen-progestin-treated female rats (19,20), and P implants in the Hab have been reported to facilitate both components of estrous behavior in one study (21) but not in another (17). In contrast, we found no consistent effect of POA or IP implants of RU 38486 on P stimulation of mating.…”

Section: Discussioncontrasting

confidence: 83%

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Antagonism of Female Sexual Behavior with Intracerebral Implants of Antiprogestin RU 38486: Correlation with Binding to Neural Progestin Receptors*

Etgen

Barfield

1986

Endocrinology

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The steroidal antiprogestin 17 beta-hydroxyl-11 beta-(4-dimethylaminophenyl)-17 alpha-(1-propynl)estra-4,9-dien-3-one (RU 38486) was administered systemically or was implanted into the ventromedial hypothalamus and other brain regions (habenula, preoptic area, interpeduncular region, in order to determine whether the compound could antagonize progesterone (P) activation of estrous responsiveness and whether the compound would exert its behavioral effects at the presumed site of P action and/or at other neural sites implicated in the regulation of female sexual behavior. RU 38486 (5 mg) administered sc 1 h before 200 micrograms P inhibited P facilitation of lordosis behavior in estrogen-primed rats. Intracerebral application of RU 38486 to the ventromedial hypothalamus reduced lordosis responses in 14 of the 25 animals tested. Similar implants in the habenula also inhibited lordosis in 5 of the 14 animals tested. Antiprogestin implants in the interpeduncular region and preoptic area were virtually without effect (1 of 7 inhibited in each group). Interactions of RU 38486 with steroid binding sites in the hypothalamus-preoptic area (HPOA) were also assessed. RU 38486 appeared to be a competitive inhibitor of progestin ([3H] R5020) binding in HPOA cytosols. Scatchard analysis of [3H]RU 38486 binding showed that when unlabeled P was used as the competitor to assess nonspecific binding, the antiprogestin bound with high affinity [dissociation constant Kd = 8.4 nm] to brain cytosols. In addition, the number of [3H]RU 38486 binding sites in HPOA cytosol increased by approximately 50% in estrogen-primed female rats. Competition studies indicated that unlabeled RU 38486 was the most effective competitor for [3H]RU 38486 binding but that P and R5020 were nearly as effective. Corticosterone, hydrocortisone, deoxycorticosterone, and triamcinolone also competed for [3H]RU 38486 binding but were somewhat less effective than the progestins. Testosterone and estradiol did not displace [3H]RU 38486 except at very high molar excesses. Thus RU 38486 appears to bind with highest affinity to HPOA progestin receptors, but it also binds to glucocorticoid receptors. These data are consistent with the interpretation that inhibition of estrous responsiveness by RU 38486 is associated with the antagonist's interference with brain progestin binding.

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Section: Discussioncontrasting

confidence: 83%

“…Because some lesion and hormone implant studies have also implicated the habenula [(Hab) Refs. [19][20][21], interpeduncular (IP) region of the midbrain (21)(22)(23)(24), and preoptic area [(POA) Ref. 25] as potential sites of P action, we also directed some RU 38486 implants at these brain regions as well.…”

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confidence: 99%

Antagonism of Female Sexual Behavior with Intracerebral Implants of Antiprogestin RU 38486: Correlation with Binding to Neural Progestin Receptors*

Etgen

Barfield

1986

Endocrinology

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“…Because of the high resolution of the macrophotographs, this method permits precise selection and three-dimensional orientation of the specimen for the intended series of sections. After embedding in Araldite, complete series of semithin sections and, where the organization of the rat habenular Benabid and Jeaugey, 1989;Daffly and Qiao, 1990;Nagao et al, 1993 Analgesia after electrical andchemical stimulation Zhou et al, 1984;Cohen and Melzack, 1985Mahieux and Benabid, 1987;Terenzi et al, 1990 Descending facilitation Huang andCheng, 1998 Modulation of acupuncture analgesia Wang et al, 1987;Takeshige et al, 1993 Reproductive behavior Presence of estrogen-concentrating cells Pfaff and Keiner, 1973;Wagner et al, 1998 Effects of progesterone and antiprogestin implant Tennent et al, 1982;Etgen and Barfield, 1986 Habenular lesions disturb female sexual and maternal behavior Rodgers and Law, 1967;Modianos et al, 1975;Corodimas et al, 1992 Site of massive electrical self stimulation Blander and Wise, 1989;Vachon and Miliaressis, 1992 Metabolic response to self stimulation Gallistel et al, 1985Further biologic behaviors Nutrition Donovick et al, 1969Sleep-waking-cycles Goldstein, 1983Weaver et al, 1989;Haun et al, 1992;Landis et al, 1993Stress responses Chastrette et al, 1991Murray et al, 1994;Wirtshafter et al, 1994Learning Dennis et al, 1991Thornton and Davies, 1991;van Wimersma Greidanus a...…”

Section: Methodsmentioning

confidence: 99%

Subnuclear organization of the rat habenular complexes

1999

J. Comp. Neurol.

205

200

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The habenular complexes represent phylogenetically constant structures in the diencephalon of all vertebrates. Available evidence suggests that this area is engaged in a variety of important biological functions, such as reproductive behaviors, central pain processing, nutrition, sleep‐wake cycles, stress responses, and learning. Based on Nissl‐stained sections, one medial nucleus and two lateral nuclei (divisions) have been widely accepted in the rat. Cytochemical, hodologic, and functional studies suggest a considerably more complex subnuclear structure. To improve our knowledge of the precise structural composition of the habenular complexes, we have systematically investigated their fine ultrastructure in the rat. Based on the detailed analysis of complete series of large, semithin sections supplemented with electron photomicrographs of selected fields, clear criteria for the delineation of five distinct subnuclei of the medial and ten subnuclei of the lateral habenular complexes were elaborated for the first time. All 15 subnuclei were reconstructed, and their dimensions were determined. A medial and lateral stria medullaris were described. Different roots of the fasciculus retroflexus were differentiated within the medial and lateral habenular complexes. The topographical relationships with respect to the adjacent habenular areas as well as to the neighboring thalamic nuclei were identified and demonstrated. The new understanding of the subnuclear organization of the habenular complexes certainly will facilitate further functional investigations. Whether the newly identified subnuclei finally will be recognized as functionally distinct awaits ongoing immunocytochemical, hodologic, and functional studies. J. Comp. Neurol. 407:130–150, 1999. © 1999 Wiley‐Liss, Inc.

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“…Several lines of evidence also suggest that the habenula is involved in female mating behavior. For example, bilateral habenula lesions reduce receptive behavior of ovariectomized, estrogen-primed female rats (Modianos et al, 1974(Modianos et al, , 1975. Other studies have reported that the habenula may play an inhibitory role in reproductive behavior.…”

Section: Discussionmentioning

confidence: 98%

Brain mast cells are influenced by chemosensory cues associated with estrus induction in female prairie voles (Microtus ochrogaster)

Kriegsfeld

Hotchkiss

Demas

et al. 2003

Hormones and Behavior

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Historically, the brain has been viewed as protected from the infiltration of peripheral hematopoietic cells by the blood-brain barrier. However, numerous immune cell types have been found in the central nervous system (CNS). Mast cells, granulocytic immune cells, are found in the CNS of birds and mammals and their numbers and location are influenced by both extrinsic and intrinsic factors, including reproductive behavior and endocrine status. The present study used female prairie voles (Microtus ochrogaster) to investigate the interactions between brain mast cells and stimuli associated with estrus induction. Unlike spontaneous ovulators such as rats and mice, female prairie voles are induced into estrus by chemosensory stimuli present in conspecific male urine. Prior to estrus induction, female voles have undetectable concentrations of estrogen that rise rapidly following exposure to a male or male urine. In the first experiment, we examined whether mast cells may be influenced by estrus induction. Female voles exposed to conspecific male urine had increased numbers of mast cells in the main olfactory bulbs and epithalamus (medial habenula), but not the thalamus or median eminence, relative to control groups. Next, to determine if this mast cell increase was the result of elevated estrogen concentrations, female voles were injected with estradiol or vehicle and brain mast cell numbers analyzed. No differences in brain mast cell numbers were observed between estradiol-injected and control females in any brain area investigated. Together, these results lend further support to the contention that mast cell numbers and/or distribution can be influenced by reproductively relevant stimuli and underscore the utility of this vole model for delineating the function of brain mast cells.

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Habenular lesions and feminine sexual behavior of ovariectomized rats: Diminished responsiveness to the synergistic effects of estrogen and progesterone.

Cited by 50 publications

References 17 publications

Antagonism of Female Sexual Behavior with Intracerebral Implants of Antiprogestin RU 38486: Correlation with Binding to Neural Progestin Receptors*

Antagonism of Female Sexual Behavior with Intracerebral Implants of Antiprogestin RU 38486: Correlation with Binding to Neural Progestin Receptors*

Subnuclear organization of the rat habenular complexes

Brain mast cells are influenced by chemosensory cues associated with estrus induction in female prairie voles (Microtus ochrogaster)

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