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L Uphouse

Publications and source records attributed to L Uphouse.

At least 55 records · Page 3Linked to original sources

Serotonin binding sites during proestrus and following estradiol treatment.

The binding of 3H-5-HT to hypothalamic, hippocampal and striatal membranes from female rats was examined. During the day of proestrus, there was a significant increase in binding from morning to evening. The increase reflected changes in both Kc and Bmax. Effects of estradiol were examined in ovariectomized rats, and changes in 3H-5-HT binding resulted from an increase in the Kd after estradiol treatment. These in vivo effects of estradiol were not seen when tissue was incubated in vitro with estradiol. However, the compound, polyvinylpyrrolidone, used in the in vitro incubation significantly increased the Kd for binding to 3H-5-HT and estradiol attenuated the increase. The potential significance of these changes to serotonin's modulation of reproductive function is discussed.

Animals↗

Diestrous treatment with lindane disrupts the female rat reproductive cycle.

Regularly cycling, adult female rats were treated during diestrus with 10, 25, 33 or 50 mg/kg lindane or with 2.5 mg/kg picrotoxin. The effects of the treatments on estrous cyclicity and on sexual behavior were examined. Doses of lindane greater than or equal to 25 mg/kg significantly increased the length of the vaginal cycle. Sexual receptivity was reduced by doses greater than or equal to 33 mg/kg, but reduction of sexual receptivity appeared to be secondary to the elongation of the estrous cycle. Most females treated with 50 mg/kg lindane failed to exhibit vaginal proestus during the duration of the experiment (6-8 d following treatment). For the lower doses, vaginal proestrus occurred later than was predicted from the cyclic history but was usually accompanied by sexual receptivity. Although lindane is reported to inhibit the GABAergic system, its reproductive effects were not mimicked by diestrous treatment with picrotoxin.

Animals↗

Sexual behavior of intact female rats after treatment with o,p'-DDT or p,p'-DDT.

Sexual behavior of adult, female rats was tested following treatment with o,p'-DDT or with p,p'-DDT during either diestrus or proestrus. Both chlorinated compounds decreased lordosis behavior, but o,p'-DDT did so only after treatment on diestrus. p,p'-DDT in contrast, decreased sexual behavior under all treatment conditions. o,p'-DDT may have altered behavior by disrupting the estrous cycle while p,p'-DDT had a major effect on the female's proceptivity and receptivity without modifying vaginal cyclicity. p,p'-DDT disrupted sexual behavior at doses as low as 25 mg/kg while 100 to 200 mg/kg o,p'-DDT were required. Since commercially prepared DDT contained a predominant proportion of p,p'-DDT, these results suggest that many reproductive effects of DDT may have resulted from p,p'-DDT rather than from o,p'-DDT.

Animals↗

Proestrous effects of chlordecone on the serotonin system.

This study concentrates on the role of the serotonin system in mediating the proestrous effects of chlordecone on female rodent sexual behavior. The pesticide was examined within the context of serotonin changes taking place on proestrous. Between morning and evening on the day of proestrus there was an increase in 3H-5-HT binding, an increase in serotonin (5-HT) and an increase in 5-hydroxyindoleacetic acid (5-HIAA). Proestrous treatment with chlordecone attenuated the increase in 5-HT and in 3H-5-HT binding but had no effect on 5-HIAA. These findings suggest that the pesticide blocked proestrous changes essential for the female's development of sexual receptivity. The 5-HT1A agonist, 8-OH-DPAT, was an inefficient competitor for 3H-5-HT binding in frontal cortex of females treated with chlordecone. It is speculated that the pesticide disrupts a balance between serotonin sites which facilitate and those which inhibit sexual behavior. Consistent with this speculation, the 5-HT agonist, quipazine, partially attenuated chlordecone's reduction of sexual behavior. Finally, the rapid effects of estradiol and chlordecone on 3H-5-HT binding sites were compared in ovariectomized female rats. These results showed no resemblance between the effects of chlordecone and those of estradiol.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Decreased rodent sexual receptivity after lindane.

Female rats were injected on the morning of proestrus with 25, 33, 50 or 75 mg/kg lindane or with 1, 2, 2.5 or 3 mg/kg picrotoxin. That evening, females were examined for lordosis behavior with a sexually experienced male. Picrotoxin had no inhibitory effects on lordosis behavior. There was a dose-dependent reduction in sexual receptivity (lordosis to mount behavior) with increasing doses of lindane. At none of the tested doses of lindane was there a total absence of lordosis behavior. However, lindane animals experienced a greater number of mounts before the first lordosis response was observed. Lindane-treated females may have required a greater amount of sensory stimulation to elicit the lordosis reflex. A majority of the lindane-treated females also failed to exhibit proceptive behavior (darting and hopping) during the mating test. The inhibitory effects of lindane on lordosis behavior are similar to previous reports of the effects of another chlorinated pesticide, chlordecone, on female sexual receptivity. Both compounds disrupt central nervous system neurotransmitters and this may account for their common attenuation of sexual behavior. Since both lindane and picrotoxin are recognized for their disturbance of the GABAergic system, these findings suggest that lindane's inhibition of sexual receptivity may not be mediated through its GABAergic action.

Animals↗

Variations in binding of [3H]5-HT to cortical membranes during the female rat estrous cycle.

The binding of [3H]5-hydroxytryptamine ([3H]5-HT) to cortical membranes was examined in female rats during diestrus, proestrus and estrus. Serotonin binding was lowest during the early afternoon of proestrus and highest during the afternoon of estrus with diestrous values in between. The high estrous values were associated with a significant increase in Bmax and a decrease in Kd. However, the increase in binding actually took place during the late afternoon of proestrus, when there was a rapid increase in binding from noon to 18.00 h. Binding remained at this elevated level throughout the next day. There were no changes in the binding of [3H]ketanserin or [3H]spiroperidol to cortical membranes during the estrous cycle, so the differential binding of [3H]5-HT is most likely the result of variations in 5-HT1 rather than 5-HT2 receptors. These observations of changes in serotonin binding in a brain area nearly devoid of sex steroid receptors suggest that the hormonal fluctuations accompanying the female estrous cycle influence brain areas other than those classically thought to regulate neuroendocrine function.

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Failure of chlordecone (Kepone) to induce behavioral estrus in adult ovariectomized rats.

The effect of chlordecone on behavioral estrus was examined in adult ovariectomized female rats. Chlordecone has been reported to resemble estrogen in altering pituitary secretions, in producing vaginal cornification, in increasing uterine weight and in competing for binding to the estrogen receptor. In the present study, 10, 25, 50 or 75 mg/kg chlordecone was substituted for estrogen in the estrogen-progesterone priming sequence used to facilitate sexual behavior of ovariectomized female rats. Sexual receptivity was measured by the number of lordosis responses exhibited by the female when mounted by a sexually active male. Chlordecone failed to substitute for estradiol in producing lordosis behavior. When female rats were given chlordecone in addition to estrogen plus progesterone, chlordecone reduced the lordosis behavior usually seen in these steroid primed animals. In further studies, chlordecone's effect on the CNS progesterone receptor was examined. Unlike estradiol, chlordecone did not induce progesterone receptors. Furthermore, chlordecone attenuated the increase in progesterone receptors seen after estradiol treatment. These findings suggest that chlordecone fails to mimic, and may actually interfere with, estrogen's facilitative effects on neurally mediated reproductive events.

Animals↗

Serotonin receptors in striatum after chlordecone treatment of adult female rats.

Serotonin receptors were examined in various brain regions of female rats 24 hours after treatment with 25, 50 or 75 mg/kg chlordecone. With each dose of chlordecone, there was a significant reduction in the specific binding of 3H-5-HT to striatum. Binding to cortex, hippocampus, hypothalamus, midbrain or brainstem did not systematically vary as a function of treatment conditions. Tremor developed in chlordecone treated female rats in a dose dependent manner with 25 mg/kg producing only slight tremor. Moderate to severe tremor was evident in rats given 75 mg/kg chlordecone. These findings support previous indications that chlordecone's action on the striatal serotoninergic system in an important component in its induction of tremor. Most such studies, however, have used relatively high doses of chlordecone so it has been difficult to determine if the serotoninergic change preceded or resulted from the tremor. The significant decrease in serotonin receptors at a dose of chlordecone which led to only slight tremor suggest that the serotoninergic change may be causally related to the production of the tremor.

Animals↗

Long-term consequences of neonatal exposure to chlordecone.

Neonate, female rats pups were injected with varying doses of chlordecone in cotton seed oil or with 1 mg chlordecone in dimethylsulfoxide. The effects of these neonatal treatments on vaginal opening, persistent vaginal estrus and adult sexual behavior were examined. Females treated with chlordecone showed earlier onset of vaginal opening and developed persistent vaginal estrus in adulthood. Sexual behavior of intact adult females was irregular but after ovariectomy and estrogen plus progesterone hormonal priming, chlordecone treated females showed normal lordosis responding. Females did not appear to have been defeminized by the neonatal chlordecone. After treatment with testosterone in adulthood, chlordecone treated females exhibited high levels of mounting behavior indicating that the neonatal treatments may have masculinized the developing hypothalamus. No significant effects of the vehicle were detected.

Animals↗

Effects of chlordecone on neuroendocrine function of female rats.

The effects of chlordecone on reproductive function was examined in adult females. Chlordecone was shown to mimic estrogen by producing persistent vaginal estrus in ovariectomized and intact females. In ovariectomized females, chlordecone reduced serum levels of luteinizing hormone (LH) and increased prolactin (PRL). In intact females, chlordecone reduced the preovulatory surges of both LH and PRL but had no effect on serum hormones of diestrous females. Chlordecone failed to mimic estrogen in priming the ovariectomized female for behavioral receptivity, and instead appeared to antagonize the priming action of estrogen. Examination of neurotransmitter changes suggested that chlordecone disrupted the usual sequence of events occurring throughout the female's estrous cycle and that this disturbance of neurotransmitter equilibrium contributed to the reproductive dysfunction. The hypothesis that chlordecone disrupts reproductive function by acting as a weak estrogen received considerable support. However, the results of several studies indicated that the neural effects of chlordecone and estradiol were not identical. We have proposed that chlordecone mimics many of the estrogen-receptor mediated neural events. However, because of the persistence of chlordecone in the organism, chlordecone fails to initiate the sequential changes which characterize estrous cyclicity.

Animals↗

Persistent vaginal estrus and serum hormones after chlordecone (kepone) treatment of adult female rats.

The effects of chlordecone on vaginal estrus and neuroendocrine responses were examined in adult ovariectomized and intact females. Persistent vaginal estrus was seen in females given 50 mg/kg or more of chlordecone. The development of vaginal estrus was similar to that seen in ovariectomized females after treatment with estrogen. Since chlordecone is known to have estrogen-like effects on the reproductive system, the persistent vaginal estrus probably results from this estrogen-like action and chlordecone's long half-life in the organism. Neuroendocrine effects of chlordecone also resembled, to some degree, estrogen's effects on pituitary secretions. Chlordecone increased serum prolactin and decreased serum luteinizing hormone (LH) in ovariectomized females 30 to 36 hr after a single exposure to 50 mg/kg of the pesticide. Basal LH levels were not altered in intact females, but the proestrous LH surge was suppressed by 36 hr after treatment. Both basal and proestrous levels of prolactin were suppressed. Unlike the effects of estrogen, serum follicle stimulating hormone was not altered by chlordecone. These results indicate an effect on the hypothalamic pituitary axis by chlordecone treatment and offer a possible explanation for the reduced fertility seen in adult females after chlordecone exposure. However, blockage of the proestrous LH surge was not obligatory for the appearance of vaginal estrus. Although chlordecone produced peripheral changes in the vaginal smear pattern as well as neuroendocrine alterations, the peripheral changes were not always indicative of the neuroendocrine events.

Animals↗

Long-term effects of behavioral testing on serum hormones and brain weight.

The effects of prior behavioral testing on endocrine function, brain weight, and neurotransmitter receptors were examined. Rats with a history of behavioral testing were significantly different from comparatively naive animals. Prior tested male and females had lower prolactin levels than nontested animals, and serum luteinizing hormone and corticosterone levels were elevated in males. In both sexes, hippocampal brain weight was greater in previously tested animals. However, estimates of brain membrane protein content and neurotransmitter receptors were unaffected by prior testing. These data suggest that prior tested animals respond as if they had experienced a history of chronic stress. Therefore, past history of the organism must be considered in studies designed to evaluate any agent's effect on neuroendocrine or neurochemical parameters.

Aging↗

Developmental changes in brain template active region chromatin.

The percentage of brain or liver chromatin in the template-active region was examined in rats of varying ages. Prenatally, there was an increase in the percentage of brain template-active region chromatin which declined near birth. After birth, the percentage of brain template-active region chromatin again increased to 3-6 days of age and then declined to adult levels at about 15 days of age. Liver exhibited a similar gestational change in the percentage of template-active region chromatin, but there was no recovery from the birth decline during postnatal development. These findings are discussed in terms of their contribution to the understanding of age-dependent changes in brain transcription.

Aging↗

Stability of CNS bindings sites under various conditions.

The effects of (1) method of sacrifice, (2) treatment of tissue and membranes, and (3) gavaging on neurotransmitter receptors were assessed. Most variables did not affect binding, but freezing of forebrain tissue decreased protein recovery and therefore estimates of binding sites per brain weight. Serotonin binding was especially sensitive to freezing to neurotoxicology is discussed.

Animals↗

Rapid effects of acrylamide on spiroperidol and serotonin binding in neural tissue.

The effects of in vivo exposure to acrylamide on 3H-spiroperidol binding to striatal and (3)5-HT binding to forebrain membranes were investigated. Rats were gavaged with 100 mg/kg acrylamide and sacrificed at various times thereafter. Rapid changes were seen with specific binding of spiroperidol increasing by 1/2 hour and 5-HT binding by 2 hours after acrylamide treatment. Although the overall effect of acrylamide was to elevate binding for at least 24 hours, binding of spiroperidol may have exhibited a biphasic profile. The possibility of dual time-dependent mechanisms involved in the effects of acrylamide is discussed.

Acrylamide↗

Corticosterone effects on rat brain template active region chromatin.

The effect of prenatal exposure to corticosterone on brain chromatin was examined. Pregnant Fischer inbred rats were administered corticosterone or saline on Days 17 and 18 of gestation and their offspring examined at 0 (day of birth), 2, 3, 4 or 6 days of age. In utero exposure to corticosterone was associated with a 24 hr delay of a developmental peak in the percentage of brain template active region chromatin. Brain and body weights of the steroid and saline-treated animals were similar, but corticosterone led to a temporary decrease in body and brain weight at 2 days of age which was reversed at 6 days of age. These results of these studies suggest an impact of corticosterone on brain gene expression.

Animals↗