Biomedical subjects

L Uphouse

Publications and source records attributed to L Uphouse.

At least 37 records · Page 2Linked to original sources

PubMed1995

Gender and estrous cycle effects of the 5-HT1A agonist, 8-OH-DPAT, on hypothalamic serotonin.

Effects of the 5-HT1A agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT; 0.04, 0.25, or 1.0 mg/kg), on hypothalamic serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), and their ratio were determined in adult male rats and in diestrous, proestrous, and estrous female rats. Consistent with its action at the somatodendritic 5-HT1A autoreceptor, 8-OH-DPAT decreased the 5-HIAA/5-HT ratio, but the decrease was least evident in proestrous females and in males. Similar to hypothalamic tissue, there was also a decline in the 5-HIAA/5-HT ratio in the hippocampus after treatment with 0.25 mg/kg 8-OH-DPAT. When ovariectomized rats were treated with oil or estradiol benzoate followed 48 h later by oil or progesterone, 0.25 mg/kg 8-OH-DPAT produced a decrease in the hypothalamic 5-HIAA/5-HT ratio in every group except those rats treated with progesterone without estrogen priming. Treatment with estradiol benzoate increased hypothalamic 5-HIAA, and both progesterone and 8-OH-DPAT reduced the metabolite to the level of the ovariectomized control. These results suggest that both estrogen and progesterone contribute to an estrous cycle modulation of the 5-HT1A somatodendritic autoreceptor.

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

PubMed1994

Agonist activation of 5-HT1A receptors in the median raphe nucleus and female rat lordosis behavior.

Proestrous rats were infused unilaterally into the median raphe nucleus with 200-2,000 ng of the 5-HT1A agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). Inhibition of the lordosis to mount ratio occurred within 15 and 10 min, respectively, following infusion with 1,000 or 2,000 ng of the drug. Infusion of 2,000 ng of the 5-HT2 agonist, (+/-)-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl (DOI), or 4,000 ng 5-HT (creatinine sulfate) failed to substantially reduce lordosis behavior.

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

PubMed1994

Estrogen-progesterone and 8-OH-DPAT attenuate the lordosis-inhibiting effects of the 5-HT1A agonist in the VMN.

Ovariectomized rats were treated for 2 consecutive weeks with 25 micrograms estradiol benzoate followed 48 h later with 500 micrograms progesterone. Bilateral infusions of 200 ng 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) into the ventromedial nucleus of the hypothalamus (VMN) inhibited female sexual behavior on the first but not the second week of hormone priming. Such attenuation on the second week of priming did not appear to result from an enhanced receptivity of the female rats since there were no differences in the L/M ratios prior to drug infusion; nor was the attenuation a consequence of infusion-induced VMN damage since neither saline nor 8-OH-DPAT preinfusions prevented the later inhibitory effects of 8-OH-DPAT on lordosis behavior. However, preinfusion with 8-OH-DPAT may have reduced the duration of the inhibition. Hormone priming (without any VMN infusion) also partially attenuated the effect of 8-OH-DPAT. Both hormone priming and treatment with 8-OH-DPAT were required to eliminate the effects of the second 8-OH-DPAT treatment. Thus, the present results suggest that gonadal hormones, alone, slightly attenuate the effects of agonist activation of 5-HT1A receptors involved in the inhibition of lordosis behavior; that agonist activation of 5-HT1A receptors also produces a slight attenuation; but that both treatments together have a robust protective action against the inhibitory effect of a 5-HT1A agonist on female lordosis behavior.

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

PubMed1994

Hypothalamic infusion of the 5-HT2/1C agonist, DOI, prevents the inhibitory actions of the 5-HT1A agonist, 8-OH-DPAT, on lordosis behavior.

Sexually receptive, intact, proestrous rats were infused bilaterally into the ventromedial nucleus of the hypothalamus (VMN) with 200 ng of the 5-HT1A agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), with 2000 ng of the 5-HT2/1C agonist, (+/-)-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl (DOI), or with both 8-OH-DPAT and DOI. Alone, VMN infusions of 8-OH-DPAT, but not DOI, inhibited lordosis behavior. When 2000 ng DOI was infused simultaneously with 8-OH-DPAT, the inhibitory effects of 8-OH-DPAT were completely abolished. These results suggest that neural sites responsible for the reported facilitatory effects of 5-HT2/1C agonists on lordosis behavior coexist in the VMN with those sites in which 5-HT1A agonists are effective in reducing lordosis behavior. In contrast to the protective action of the 5-HT2/1C receptor agonist following VMN infusion, no protection was seen when both DOI and 8-OH-DPAT were administered intraperitoneally. Thus, the interaction of these two receptor subtypes in the control of lordosis behavior may be different in regions outside the VMN.

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

PubMed1993

Female sexual behavior following intracerebral infusion of the 5-HT1A agonist, 8-OH-DPAT, into the medial preoptic area.

The effects of intracerebral infusions of the 5-HT1A agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), on sexual behaviors of intact, proestrous rats were examined. When administered into either the rostral or the caudal portions of the medial preoptic area (mPOA), bilateral infusions of 200, 500, or 2,000 ng of 8-OH-DPAT reduced lordosis behavior (e.g. the lordosis/mount ratio; L/M) and increased the female's resistance to the male's attempts to mount. Infusions within the mid-rostrocaudal mPOA failed to suppress lordosis behavior but were as effective as the rostral or caudal infusions in the elicitation of resistive behavior. A reduction in the L/M ratio was usually accompanied by a slight decline in the quality of the lordosis reflex; proceptivity, as evidenced by the occurrence of hopping and darting behavior, was not consistently reduced by 8-OH-DPAT. In fact, 4 out of 7 rats that received mid-rostrocaudal infusions of 8-OH-DPAT showed a "frenzied" accentuation of hopping and darting behavior. These results suggest that 5-HT1A receptors in the mPOA play an important role in several components of female sexual behavior. The identification of a rostral and caudal location of mPOA sites where 8-OH-DPAT suppressed lordosis behavior is consistent with the organization of 5-HT fibers in the mPOA and with ventromedial hypothalamic (VMN) input into the mPOA.

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

PubMed1993

Inhibitory effects of the 5-HT1A agonists, 5-hydroxy- and 5-methoxy-(3-di-n-propylamino)chroman, on female lordosis behavior.

Sexually receptive, intact, proestrous rats were infused bilaterally into the ventromedial nucleus of the hypothalamus with one of several serotonin (5-HT) agonists and with the endogenous ligand, 5-HT. Serotonin (2000 ng) and the 5-HT1A agonists, 8-hydroxy-2-(di-n-propylamino)tetralin [8-OH-DPAT (200 ng)], 5-methoxy-3-(di-n-propylamino)chroman [5-MEO-DPAC (200-2000 ng)] and 5-hydroxy-3-(N-di-n-propylamino)chroman [5-OH-DPAC (200-2000 ng)] inhibited female lordosis behavior within 10 min of the infusion. The rank order of the effectiveness of these compounds was 8-OH-DPAT > 5-OH-DPAC > or = 5-MEO-DPAC > 5-HT. The nonselective 5-HT agonist, 1-(m-trifluoromethyl) piperazine [TFMPP (2000 ng)], did not reduce lordosis behavior. In addition to their reduction of lordosis behavior, the 5-HT1A agonists elicited resistive behavior toward the male's attempts to mount. There were minimal effects of the 5-HT1A agonists on either quality of the lordosis reflex or on proceptivity. However, rats pretreated with TFMPP and infused with 8-OH-DPAT 1 hr later, did show a transient suppression of lordosis quality. These results provide further evidence that the ventromedial nucleus of the hypothalamus contains 5-HT1A sites, the activation of which reduces lordosis behavior in regularly cycling, proestrous rats.

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

PubMed1992

Intracerebral actions of the 5-HT1A agonists, 8-OH-DPAT and buspirone and of the 5-HT1A partial agonist/antagonist, NAN-190, on female sexual behavior.

Proestrous rats were infused intracerebrally with 50-1000 ng 8-OH-DPAT, 500 or 2000 ng buspirone or 125-500 ng NAN-190. For each drug, bilateral infusions into the mediobasal hypothalamus inhibited female lordosis behavior and proceptivity and initiated resistive behavior. The effects of the drugs were evident within 5-20 min of infusion and generally lasted for 1-2 hr. The effective sites for 5-HT1A-mediated inhibition of sexual behavior were most concentrated in the ventromedial nucleus of the hypothalamus. Cannulae sites anterior, posterior or dorsal to the ventromedial nucleus or clearly within the IIIrd ventricle were less effective at disrupting lordosis behavior. The inhibition of sexual behavior, following 8-OH-DPAT occurred in a dose-dependent manner and appeared to include the loss of motivation of the female to mate. Buspirone produced similar, but quantitatively smaller, effects on lordosis behavior. NAN-190 slightly, but significantly, suppressed lordosis behavior after either intracerebral or intraperitoneal injection and substantially increased resistive behavior. These results suggest that the inhibition of lordosis behavior, following treatment with 5-HT1A agonists, include an action within the ventromedial nucleus. Moreover, 5-HT1A receptors in this area appear to play a functionally important role in the modulation of the female's "willingness" to mate.

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

PubMed1992

8-OH-DPAT in the midbrain central gray inhibits lordosis behavior.

Sexually receptive female rats were infused intracranially with 500-2,000 ng 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) into the midbrain central gray (MCG), in the vicinity of the dorsal raphe nucleus (DRN), or directly into the DRN. When cannulae were located within the DRN, there was little evidence of change in lordosis behavior but a decrease in locomotor activity was commonly observed. In contrast, when cannulae were located anterior, ventromedial, or lateral to the DRN inhibition of lordosis behavior was rapid and robust. Both the lordosis-to-mount ratio (L/M) and the quality of the lordosis reflex were reduced following the infusion. The MCG receives lordosis-facilitating input from the ventromedial nucleus of the hypothalamus and from ascending sensory pathways and contributes information to descending motor systems involved in the lordosis response. Thus, the MCG is a critical link in the completion of the estrogen-dependent lordosis reflex. The present results suggest that 5-hydroxytryptamine1A receptors in the MCG prevent the completion of this reflex.

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

PubMed1992

Estradiol modulation of the hyperphagia induced by the 5-HT1A agonist, 8-OH-DPAT.

Ovariectomized rats were primed with sesame oil or estradiol benzoate followed 48 h later by either sesame oil or progesterone. Four hours later, rats were treated with either saline or 0.25 mg/kg 8-hydroxy-2-9(di-n-propylamino)tetralin (8-OH-DPAT). Rats were allowed to eat for 4 h after this final treatment. Animals in all hormonal conditions showed hyperphagia following 8-OH-DPAT. However, the hyperphagia was significantly attenuated by pretreatment with estradiol benzoate. There was no effect of progesterone on the hyperphagic response. These results suggest that previous findings of an estrous cycle modulation of the hyperphagic response to 8-OH-DPAT arise from the modulatory effects of estradiol, and not progesterone, during the female reproductive cycle.

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

PubMed1992

Disruption of female rat vaginal cyclicity by daily treatment with imipramine.

Intact, adult female rats were injected for 21 days with 10 mg/kg of the tricyclic antidepressant imipramine. During this time, there was almost total suppression of reproductive cyclicity as indicated by the absence of vaginal proestrus and by the absence of sexual receptivity. However, there was no evidence for a permanent disturbance in the female reproductive system. When treatment with imipramine was terminated, vaginal cyclicity resumed within the next 2 to 8 days. The generality of the current findings to other antidepressants or to the human female is currently unknown. However, since human females are the primary consumers of antidepressants, caution should be exercised when females are given antidepressant therapy.

Animals↗

PubMed1992

Effects of chlordecone on food intake and body weight in the male rat.

The effects of the chlorinated pesticide chlordecone on food intake, body weight, and water intake were examined in adult male rats. Chlordecone treatment produced a dose dependent suppression of food intake. Loss of body weight accompanied the reduced food intake. However, chlordecone did not suppress water intake. Chlordecone treated animals maintained on a liquid diet also demonstrated reduced food intake, suggesting that chlordecone has a specific effect on feeding behavior and not a general effect on ingestive behaviors. The potential contribution of chlordecone-induced tremor to the suppressed food intake and the loss of body weight was considered. When treatment occurred immediately before a 24 hr fast, controls and animals given 75 mg/kg showed no differences in the body weight decline, even though tremor occurred in the pesticide-treated rats. Thus, it is unlikely that tremor alone produced the body weight loss observed in the present experiment. Similarly, animals were capable of initiating eating behavior even though tremor was present. In addition, chlordecone treatment inhibited food intake within 2 hr. Consequently, these results suggest that chlordecone suppresses food intake which in turn produces the decline in body weight.

Animals↗

PubMed1991

Chlordecone (Kepone) on the night of proestrus inhibits female sexual behavior in CDF-344 rats.

The effect of the estrogen-like chlorinated pesticide chlordecone (Kepone) on sexual behavior was examined in proestrous rats following treatment with 25, 50, or 75 mg/kg chlordecone. In most animals, sexual behavior, both receptivity and proceptivity, was reduced within 60 min following the higher dosage of chlordecone. Reduced sexual receptivity occurred more slowly with 50 mg/kg chlordecone (usually within 180 min) and no reduction was seen following 25 mg/kg chlordecone. The reduced sexual behavior after chlordecone treatment preceded the onset of marked chlordecone-induced tremor. A group of rats treated with 75 mg/kg chlordecone was euthanized at the time that behavioral inhibition began to develop. The content of serotonin, norepinephrine, and their principal metabolites was determined by high-performance liquid chromatography of extracts of brain tissue of these animals. In hypothalamus, increases in serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) content, and a decrease in the level of norepinephrine (NE), were detected in chlordecone-treated rats relative to matched controls which received vehicle. The content of 5-HT was also increased in preoptic area of chlordecone-treated females. The content of the catecholamine metabolite, 3,4-dihydroxy-phenylacetic acid, was unaffected by chlordecone in either part of brain. These are the first observations of the parallel effects of chlordecone on receptive and proceptive behaviors, and on neurochemistry, in female rats; the results demonstrate short-latency effects of the pesticide treatment on the CNS events that mediate female reproductive behavior. Results of previous studies had led to the suggestion that chlordecone's inhibition of sexual behaviors resulted from its interaction with the intracellular estrogen receptor. However, the rapidity of the inhibition during the period of ongoing sexual behavior makes it unlikely that the inhibition is mediated by the pesticide's action at the intracellular estrogen receptor. Because of the importance of sexual behaviors to reproductive fitness, the current results indicate that nonsteroidal, behavioral mechanisms could contribute to chlordecone's neuroreproductive toxicity.

Analysis of Variance↗

PubMed1991

Gender and estrous cycle differences in the response to the 5-HT1A agonist 8-OH-DPAT.

The effects of the 5-HT1A agonist, 8-hydroxy-2-9(di-n-propylamino)tetralin (8-OH-DPAT) on eating behavior and on rectal temperature were examined in adult male rats and in diestrous, proestrous, and estrous female rats. The 5-HT1A agonist produced evidence of hyperphagia at some dose (0.125, 0.25, 0.5 and 1.0 mg/kg) in all groups examined. However, hyperphagia was most evident in diestrous females and least evident in proestrous and estrous rats. These findings are interpreted as an estrous cycle modulation of somatodendritic 5-HT1A autoreceptors. The hypothermic response to 8-OH-DPAT was present in all females and at all doses of 8-OH-DPAT (0.1, 0.25 and 0.5 mg/kg). These findings suggest that postsynaptic 5-HT1A sites involved in 8-OH-DPAT-induced hypothermia do not vary during the estrous cycle. However, males showed less hypothermia following 8-OH-DPAT than did females. The gender difference was evidenced primarily as a slower onset of hypothermia in males treated with the lower doses of the drug.

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

PubMed1991

Effects of the 5-HT1A agonist, 8-OH-DPAT, on sexual behaviors of the proestrous rat.

The effects of the 5-HT1A agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), were examined in intact, proestrous rats. Although this compound has been reported to inhibit sexual receptivity of hormonally primed, ovariectomized rats, this is the first report of its effect in intact females. After intraperitoneal treatment with 8-OH-DPAT (0.01 to 0.25 mg/kg), there was a dose-dependent suppression of lordosis behavior. The inhibition occurred within 10-15 min after the higher doses and lasted at least an hour after treatment. When females were treated with 1 mg/kg trifluoromethylphenyl piperazine (TFMPP) 30 min prior to treatment with 0.1 mg/kg 8-OH-DPAT, females recovered more rapidly from the inhibitory effects of 8-OH-DPAT. After bilateral, intrahypothalamic infusion of 50 to 1000 ng 8-OH-DPAT, inhibition of sexual behavior resembled that seen following systemic treatment with 0.1 mg/kg 8-OH-DPAT, females recovered more rapidly from the inhibitory effects of 8-OH-DPAT. After bilateral, intrahypothalamic infusion of 50 to 1000 ng 8-OH-DPAT, inhibition of sexual behavior resembled that seen following systemic treatment. Cannula locations in the ventromedial hypothalamus, but not the posterior hypothalamus, produced rapid inhibition of lordosis behavior. Both the frequency and the quality of lordosis behavior were reduced within 5 to 10 min after bilateral infusion of 200 to 1000 ng (but not 50 ng) 8-OH-DPAT, and females often successfully avoided attempted mounts by the male. These results suggest that activation of ventromedial hypothalamic 5-HT1A receptors reduces lordosis behavior.

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

PubMed1991

Vaginal cyclicity, sexual receptivity, and eating behavior of the female rat following treatment with chlordecone.

The effects of 25, 50, or 75 mg/kg chlordecone on vaginal and behavioral estrus were examined following treatment of intact rats during estrus, diestrus 1, or diestrus 2. Chlordecone accelerated vaginal estrus, but sexual behavior was eliminated, delayed, or reduced. Chlordecone treatment led to the presence of vaginal estrus within 2 days, but reduced or eliminated sexual behavior on the evening of predicted proestrus. Of the females that received chlordecone, 20% to 50% showed some behavior on the day after the evening of predicted proestrus and 20% to 35% never showed behavior during the 8-day observation period. Although the lordosis to mount ratio was still reduced, the occurrence of behavior a day late suggested that the pesticide had delayed behavioral estrus. Chlordecone also rapidly suppressed food intake and led to a significant decline in body weight; these nutritional factors could have contributed to the disrupted estrous cycle. Some support for this possibility was derived from a reduced sexual receptivity on the evening of proestrus when the caloric intake of untreated female rats was matched to that of the chlordecone treated animals. However, the effects of caloric reduction on proestrous lordosis behavior were less robust than seen following chlordecone. Chlordecone treatment on diestrus 2 reduced the number of progesterone receptors in uterine tissue of females on the predicted day of proestrus. This suggested that the tissue sensitivity to circulating levels of progesterone would be reduced within 2 days after chlordecone treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

Serotonergic changes following proestrous treatment with p,p'-DDT.

The effects of 25 and 75 mg/kg p,p'-DDT on the CNS serotonergic system were examined in proestrous female rats. Females were treated with p,p'-DDT on the morning of proestrus and were sacrificed that evening. Levels of serotonin (5-HT) and its major metabolite, 5-hydroxyindoleacetic acid (5-HIAA), were examined in cortex, hippocampus, hypothalamus and preoptic areas. The binding of 3'-8-OH-DPAT [2-hydroxy-2-N, N-(di-propylamino)-tetralin], an agonist for 5-HT1A receptors, was examined in hippocampus and frontal cortex. P,p'-DDT decreased the level of 5-HT in frontal cortex and hippocampus. Elevations in 5-HIAA were present in the hypothalamus but only at the higher dose of p,p'-DDT. The dose of 25 mg/kg p,p'-DDT produced an increase in the Bmax for 3H-8-OH-DPAT binding to frontal cortical and hippocampal membranes. Membrane preparations from females given 75 mg/kg p,p'-DDT fell into two categories. Some were similar to the control but with a slightly higher Kd; others could not be analyzed by traditional linear or nonlinear regression procedures because they showed a constant proportion of bound label, independent of the concentration of 3H-ligand in the reaction. In vitro, p,p'-DDT did not compete with 3H-8-OH-DPAT for binding to cortical membranes so it is unlikely that residual pesticide in the membrane preparation accounted for the binding results. These binding results are particularly interesting because, in previous studies, the dose of 25 mg/kg p,p'-DDT was shown to be more potent than 75 mg/kg p,p'-DDT in reducing female rodent lordosis behavior.(ABSTRACT TRUNCATED AT 250 WORDS)

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

PubMed1989

Effects of chlordecone on progesterone receptors in immature and adult rats.

The ability of the chlorinated pesticide chlordecone to induce the CNS (hypothalamus and preoptic area) plus pituitary and uterine progesterone receptors was examined in CDF-344 female rats following treatment with 25 micrograms estradiol or with 75 mg/kg chlordecone. In adult ovariectomized rats and in intact immature rats, estradiol increased progesterone receptors in neural and uterine tissues. This was in contrast to the effect of chlordecone. Chlordecone treatment of rats induced progesterone receptors in uterus of immature rats, but not in uterus of ovariectomized adult rats. In neither age group were CNS plus pituitary progesterone receptors increased following chlordecone treatment. These results suggest that the pesticide fails to mimic an estradiol-dependent event of substantial consequence to the CNS regulation of female reproductive functioning. These findings are discussed in terms of the possibility that chlordecone may, rather than mimicking, have the potential to attenuate estradiol's CNS effects. In addition to the effects of chlordecone on progesterone receptors, the effects of chlordecone in combination with estradiol were examined. Three temporal combinations between chlordecone and estradiol, which produce different effects on sexual behavior, were examined. The objective was to determine if chlordecone's inhibition of sexual behavior may have resulted from an attenuation of estradiol's production of CNS progesterone receptors. Chlordecone did not attenuate estradiol's elevation of CNS progesterone receptors under any of the three treatment conditions. Collectively, these studies demonstrate that chlordecone fails to mimic a well-defined and functionally significant effect of estradiol's interaction with the CNS estradiol receptor. However, they also suggest that the pesticide's inhibition of CNS estradiol events does not depend upon its attenuation of estradiol's induction of the CNS progesterone-receptor.

Animals↗

PubMed1989

Estradiol and chlordecone interactions with the estradiol receptor.

The in vivo and in vitro effects of the chlorinated pesticide, chlordecone, on the estradiol receptor of adult ovariectomized CDF-344 rats were examined. Chlordecone's competition with [3H]estradiol for binding to the estradiol receptor in vitro was similar whether receptors were derived from neural or uterine tissue. In vivo, chlordecone led to nuclear retention of estradiol receptors in both tissues, but in comparison to estradiol, the latency for such retention was slower following chlordecone. Nevertheless, chlordecone- and estradiol-treated animals eventually achieved the same degree of nuclear retention in uterine tissue. In brain, estradiol-like levels of nuclear retention were never found in chlordecone-treated females. Estradiol receptor replenishment following chlordecone or estradiol was similar in uterine tissue but not in brain. Chlordecone's lesser ability to mimic estradiol's receptor dynamics in the brain may contribute to the apparent tissue differences in chlordecone's estrogenicity.

Animals↗