Thermoregulation in hyperthyroid rats: mechanism underlying the lack of hypothermic response to morphine in hyperthyroid animals

Previous experiments in our laboratory demonstrated that morphine, at doses which produced pronounced hypothermia in normal rats, not only failed to decrease but instead increased body temperature in thyroxine-treated animals. The present studies were undertaken to further investigate these initial findings. In animals treated chronically with subcutaneous thyroxine, basal body temperatures were elevated and morphine induced only hyperthermia whether given subcutaneously (10 mg/kg) or centrally (30 micrograms) into the anterior hypothalamus. Basal oxygen consumption, which reflects metabolic heat production, was significantly elevated when compared to controls. In response to morphine, control animals showed decreased oxygen consumption while thyroxine-treated animals showed a slight increase. In both groups of animals, changes in core temperatures reflected changes in oxygen consumption. These results indicate that hyperthyroid animals fail to decrease body temperature in response to morphine because they are unable to decrease metabolic heat production. Morphine, acting at central hypothalamic sites, reduces heat production in normal animals, but in thyroxine-treated animals morphine cannot overcome the increased thermogenesis.     

Development and adult pituitary-adrenal function in female rats injected with morphine during different postnatal periods

Developmental, neuroendocrine and behavioral effects of early morphine addiction in female rat pups were investigated. compared with controls, body weights of morphine-injected animals, regardless of treatment age, were depressed during treatment and remained depressed for periods up to 49 days; growth rates of these animals were decreased during drug treatment but temporarily surpassed those of controls following termination of morphine administration. Delayed eye opening and early vaginal opening occurred in some of the animals administered morphine before Day 14. Behaviorally, animals treated with the narcotic from Days 15–21 showed impaired activity in the open field test; all animals, in any early morphine treatment group, showed normal resting pituitary-adrenal activity at 30 days of age and showed no neuroendocrine signs of protracted dependence. However, rats neonatally narcotic-treated on Days 15–21 showed a decreased corticosterone rise in response to morphine challenge of 30 mg/kg for as late as Day 62. The persistence of the weight and endocrine effects suggest that exposure of the immature female rat to morphine results in prolonged morphine-specific alteration of brain mechanisms concerned with behavioral and neuroendocrine processes and supports the suitability of using a rat model to study long-term effects of neonatal narcotic addiction.     

Radiation effects on diamine oxidase activities in intestine and plasma of the rat

Diamine oxidase (DAO; EC 1.4.3.6) activity was measured in plasma and in ileal tissue homogenates prepared from male Sprague-Dawley rats euthanized at 1-15 days after acute whole-body irradiation with 14.5-MeV electrons. Animals irradiated with 1 Gy showed no diminution in plasma and ileal DAO activities through Day 13 relative to nonirradiated controls. Animals irradiated with 5, 10, and 12 Gy displayed marked declines in ileal DAO activity, with levels reaching a nadir on Day 3. This was paralleled by a decrease in plasma DAO activity in all three dose groups. Recovery of ileal and plasma DAO levels was later seen as early as Day 4 in animals irradiated with 5- and 10-Gy doses, but animals receiving 12 Gy did not survive beyond Day 3. The relationship between radiation dose and levels of plasma and ileal DAO on Day 3, the time of maximum decrease at all doses, was also investigated. Ileal DAO activity decreased almost linearly between 2 and 8 Gy. Plasma DAO activity closely paralleled the dose dependency of the ileal levels. These data suggest that plasma DAO activity might be useful as a biologic marker of intestinal epithelial injury and recovery after acute radiation exposure.     

Reduced tolerance to morphine thermoregulatory effects in senescent rats

Age-related differences in the thermoregulatory response to morphine have been shown in rats. To determine if these age-related differences would be reflected in the acquisition of tolerance, we studied morphine tolerance induced by either a single morphine dose or implantation of a morphine pellet. precipitated withdrawal was also analyzed by inducing withdrawal with naloxone in morphine-pelleted rats. Senescent (26 or 27 month old), mature (10 or 11 month old) and young (3 or 4 month old) male Fischer 344 rats were restrained and changes in rectal temperature were monitored for six hours after morphine administration. Only mature and young rats exhibited increased hyperthermic responses to a second low dose of morphine (5 mg/kg s.c.). Only young rats became tolerant after a single higher morphine dose (25 mg/kg s.c.). All age groups showed tolerance three days after morphine pellet implantation. Hypothermia was equivalent in all age groups when withdrawal was induced by naloxone in morphine-pelleted rats. These results indicate that older rats were more resistant to the acquisition of tolerance to the thermic effects of morphine; however; with continued morphine treatment, rats became tolerant regardless of age.     

The effects of nonadecafluoro-n-decanoic acid on serum retinol and hepatic retinyl palmitate hydrolase activity in male Sprague-Dawley rats

The effects of nonadecafluoro-n-decanoic acid (NDFDA) on serum retinol levels and hepatic retinyl palmitate hydrolase (RPH) activity were investigated in male Sprague-Dawley rats given a single intraperitoneal (IP) dose of 0, 50, or 100 mg/kg NDFDA and sacrificed at two, eight, or 11 days. Treated animals exhibited depressed serum retinol levels, lymphoid involution, and failure to gain weight in proportion to the dose. Hepatic RPH activities were depressed in both treatment groups at all time points and correlated with serum retinol levels. Hepatic retinol levels were also depressed by Day 11. Extraction of hepatic homogenates with acetone removed NDFDA and increased RPH activities twofold and threefold for the low- and high-dose groups, respectively. Analysis of partially purified RPH showed both NDFDA and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) to be noncompetitive inhibitors: KI = 450 and 750 microM, respectively. We conclude that NDFDA causes a decrease in the mobilization of vitamin A from the liver by noncompetitive inhibition of RPH.     

Serum erythropoietic activity in acute anemia--an animal model

Serum erythropoietic activity and reticulocyte response to anemia were investigated using a rabbit model. In hemolytic anemia, induced by injections of phenylhydrazine on Day 0 the hemoglobin reached a nadir (mean, 6.23 g/dl) on Day 4 when SEA was maximal (mean, 765 mU/ml). In animals venesected on Day 0 and Day 1 to produce anemia of equal severity, the SEA was maximal (mean 235 mU/ml) on Day 2. In both groups the reticulocyte response peaked on Day 7--at 34% for the hemolytic group and 21% for the venesected group. The 2,3-diphosphoglycerate, measured on Day 4, was significantly reduced in the PHZ-treated group. In the venesected group the 2,3-DPG increased between Day 0 and Day 4. There were no concurrent changes in acid-base balance. These results imply that the degree of anemia is only one of the factors which influence the level of circulating SEA.     

Effect of dinoprost and cloprostenol on serum nitric oxide and corpus luteum blood flow during luteolysis in ewes

In this study we compared the effect of dinoprost and cloprostenol on changes of corpus luteum blood flow during luteolysis. Ten nonlactating cyclic ewes were synchronized with double PGF_2α injections 11 days apart. At Day 10, the animals were classified into 2 groups and received the third dose of PGF_2α after confirmation of the presence of a mature CL. The first group received (12.5 mg/im) dinoprost and the second group received (250 μg/im) cloprostenol. A color Doppler ultrasound scan was performed by the same operator according to the following timeline: 0, 0.5, 1, 2, 4, 6, 12, and 24 hours, then every 24 hours until Day 4). The size, morphology, and blood flow of the CL was evaluated during the regression. The results showed that regression of the CL did not differ between the dinoprost and cloprostenol groups. There was no significant effect on diameter of the CL in both groups, though the size of the CL decreased gradually and slowly. Pretreatment progesterone concentration did not differ between groups. The results showed that the nitric oxide level was significantly increased within half an hour after the dinoprost treatment, and was significantly decreased in the cloprostenol group after half an hour. The blood velocity was increased significantly half an hour after the dinoprost treatment and it was decreased in the cloprostenol-treated group. In conclusion, both cloprostenol and dinoprost affect CL by controlling the nitric oxide level and blood supply of the CL via different mechanisms to induce luteolysis.     

The role of contextual cues on counterirritation in the development process of analgesic tolerance to morphine

Tolerance to morphine analgesia was determined by daily exposing rats either to the same box or different boxes during repeated administration of formalin (2.5%, 0.4 mL/body, sc) and morphine (5 mg/kg, sc). The analgesic effect was determined daily for four consecutive days by exposing rats to either the same box or different boxes, and the process of tolerance development was assessed by a hot plate test (52.5 degrees C). The rats were divided into four groups: one group received formalin and morphine in the same context (Group FM-Same), one group in the different context (Group FM-Diff), one group received saline and morphine in the same context (Group SM-Same), two groups received formalin in the same or different contexts (Groups FS-Same or FS-Diff), and one group received saline in the same context (Group SS-Same). The response latency of Group SM-Same was decreased from Day 2 to a level similar to that of Group SS-Same on Day 4, while that of FM-Same decreased more slowly. The latency of Group FM-Diff maintained the level of Day 2 until Day 4, being significantly longer than that of FM-Same. In the Extinction Phase, all rats received formalin and saline injections in the same box they had been exposed to on Day 1. On the first day, hyperalgesia was evident in Group SM-Same alone. In the Re-test Phase, the rats underwent a second morphine injection, and showed recovery from tolerance. These results indicate that formalin-induced chronic stress pain reduces tolerance development to morphine, and the mutual influence of pain, counterirritation, between formalin and hot-plate, facilitates the effect of contextual cues by inhibiting an associative learning.     

Changes in succinic dehydrogenase activity in the central nervous system of mice during morphine dependence development, withdrawal and naloxone treatment

The possible role of succinic dehydrogenase (SD) in producing physical dependence to morphine by affecting tissue respiration was investigated in Swiss albino mice during the development of morphine tolerance through a period of addiction and naloxone withdrawal therapy. Tolerance and physical dependence were induced by injecting the mice with morphine sulfate subcutaneously at 8-hour intervals, increasing the dose from 10 mg/kg BW every 24 h for 15 days. The animals were considered to be addicted when they were able to tolerate an otherwise lethal dose of 150 mg/kg 3 times a day. Results indicated that succinic dehydrogenase was inhibited throughout the 15-day period of morphine administration and that this effect was greatest in tolerant animals. Increasing the dose and duration of treatment did not cause further decreases in enzyme activity; instead, after 15 days levels of enzyme activity increased in addicted animals compared with tolerant mice. Furthermore, morphine abstinence for 2 days, markedly increased the levels of SD activity, while 6 days of abstinence had little effect. Naloxone withdrawal at each stage was associated with increased SD activity, but the increase was significant only in tolerant mice.     

Endocrine influences on the actions of morphine: IV. Effects of sex and strain

The antinociceptive and temperature responses to morphine were compared in male and female rats from two different strains. Males of both the Sprague-Dawley and Wistar-Furth strains were slightly more responsive to the acute actions of morphine than were females of the same strain. However, Wistar-Furth animals required approximately twice the dose of morphine to display equivalent antinociceptive responses and four times the dose of display equivalent hypothermic responses when compared with Sprague-Dawley animals. During chronic morphine treatment, the development of tolerance was slightly more rapid in males than in females and in Sprague-Dawley animals than in Wistar-Furth animals. Gonadal hormones also influenced morphine responses. Ovariectomized rats were significantly more responsive acutely to morphine and developed tolerance less rapidly than estradiol-treated females. However, alterations of gonadal hormones in males did not affect morphine responses. These results indicate that morphine responses vary considerably between strains of animals and are influenced by gonadal hormones of females, but not of males.     

The effect of subluteal levels of exogenous progesterone on follicular dynamics and endocrine patterns during early luteal phase of the ewe

Nineteen Corriedale ewes were treated with an im dose of a PGF2alpha during the luteal phase to synchronize estrus. After ovulation had been detected by using ultrasonography (Day 0); the ewes were randomly assigned to 2 different groups. In 11 ewes a CIDR, which had previously been used for 10 d, was inserted on the fourth day after ovulation. The ewes then received a dose of PGF2alpha on Day 5 to induce luteolysis. The CIDR remained in place until the end of the experiment (Day 9). Control ewes (n = 8) received no treatment. Blood samples were taken daily for estradiol, progesterone and FSH determinations. In the untreated ewes, 2 follicular waves were detected in all of the animals throughout the monitoring period, with a mean wave interval of 4.5 d. The total number of follicles which were > or =2 mm decreased from Day 0 to Day 4 (8.8+/-1.0 to 5.3+/-0.6; P< or =0.05) and then increased at Day 7 (7.5+/-0.9; P< or =0.05). The growth profiles of both the largest and the second largest follicles of Wave 1 showed significant divergence, while no divergence was observed in Wave 2. Serum estradiol concentrations decreased significantly from the day before to the day of ovulation and then increased again during the growing phase of the largest follicle of Wave 1. Concentrations of FSH were high on the day of emergence of both waves, but while a significant decline was observed after emergence in Wave 1, the levels remained high in Wave 2. In 8 of the 11 treated ewes, the largest follicle of Wave 1 was still present on the ninth day after ovulation (persistent follicle). In the other 3 ewes, the largest follicle of Wave 1 was already regressing on the day that the treatment was administered, and the largest follicle that was present on Day 9 originated from Wave 2 (nonpersistent follicle). In persistent follicle ewes, the largest follicle of Wave 1 prolonged its lifespan significantly, attaining the maximum diameter (Day 8.1+/-0.8) later than in untreated (Day 3.0+/-0.4) and nonpersisted follicle ewes (Day 2.0+/-0.6). The total number of follicles decreased in persistent follicle ewes between Day 0 and Day 4 (7.9+/-1.5 to 4.5+/-0.5, respectively; P< or =0.05) and remained low until the end of the experiment. Progesterone concentrations (nmol/L) between Days 6 and 9 were significantly different between untreated and persistent follicle ewes (12.8+/-1.0 vs. 9.4+/-1.0, P< or =0.02). The present study confirms that the largest follicle of Wave 1 is dominant in the ewe and that subluteal progesterone concentrations can prolong its lifespan and extend this dominance.     

Teratogenic, biochemical, and histological studies with mice prenatally exposed to 2.45-GHz microwave radiation

Pregnant CD-1 mice were exposed to 2.45-GHz continuous wave microwave radiation at an incident power density of 30 mW/cm2. The local specific absorption rate near the uterine area (deep colonic location), as determined from time-temperature profiles measured with a Vitek thermistor probe, was 40.2 mW/g. Groups of mice were exposed 8 hr per day through Days 1-6 or 6-15 of pregnancy. Other groups of animals were exposed to an elevated ambient temperature of 31 degrees C which increased the colonic temperature 2.3 degrees C, the same as that produced by the microwaves. Sham-irradiated groups of animals were treated exactly the same as the microwave-exposed animals. For the two conditions, temperature exposed and sham exposed, two groups of animals were used. One group was handled in the same manner as the microwave-irradiated group and the other group was not handled so as to evaluate the effects of stressing the animals by handling. Eleven groups of animals were used in the complete study: five groups for gestational Days 1-6, five groups for gestational Days 6-15, and one group of cage control animals. On Day 18 of gestation the dams of all experimental groups were sacrificed and their reproductive status was determined. The fetuses were examined for visceral and skeletal alterations. Brain cholinesterase activity and histology were evaluated in the groups exposed on Days 6-15. The results show that microwave radiation increases embryo lethality at the early stages of gestation (exposure Days 1-6). Fetal toxicity and teratogenicity were not significantly increased by exposure to microwaves on either Days 1-6 or 6-15 of gestation. Cholinesterase activity and histology of the brain of 18-day-old fetuses were not adversely affected.     

Variations in the vulvar temperature of sows during proestrus and estrus as determined by infrared thermography and its relation to ovulation

The prediction of ovulation time is one of the most important and yet difficult processes in pig production, and it has a considerable impact on the fertility of the herd and litter size. The objective of this study was to assess the vulvar skin temperature of sows during proestrus and estrus using infrared thermography and to establish a possible relationship between the variations in vulvar temperature and ovulation. The experimental group comprised 36 crossbred Large White × Landrace females, of which 6 were gilts and 30 were multiparous sows. Estrus was detected twice daily and the temperature was obtained every 6 hours from the vulvar area and from two control points in the gluteal area (Gluteal skin temperature [GST]). A third variable, vulvar–gluteal temperature (VGT) was obtained from the difference between the vulvar skin temperature and the GST values. The animals were divided into two subgroups: group A consisting of 11 animals with estrus detected at 6:00 AM, Day 4 postweaning, and group B comprising seven animals with estrus detected at 6:00 AM, Day 5 post-weaning. Both groups showed a similar trend in the VGT. The VGT increased during the proestrus, reaching a peak 24 hours before estrus in group A and 48 hours before estrus in group B. The VGT then decreased markedly reaching the lowest value in groups A and B, respectively, 12 and 6 hours after estrus. Although the time of ovulation was only estimated on the basis of a literature review, the matching between the temporal variations of the VGT values and the predicted time of the peak of estradiol secretion that ultimately leads to the ovulation processes suggests that the VGT values represent a potential predictive marker of the ovulatory events.     

Observations on variability in LH release and fertility during oestrus in the domestic cat (Felis catus)

Hormonal changes, behaviour, ovulation and fertility were examined in response to coitus at two different times during oestrus in the female domestic cat housed in conditions of natural light (N = 13). On Day 2 or Day 4/5 of oestrus females were allowed 1 copulation in 15 min (single matings) or 2-3 copulations in 30 min (multiple matings). Plasma LH, oestradiol-17 beta and progesterone concentrations during the 24-h period after coitus were measured by radioimmunoassay; ovulation was assumed to have occurred if progesterone values were elevated 7-30 days after coitus. With the exception of 2 out of 3 animals receiving single matings on Day 2 of oestrus, all animals showed subsequent elevated progesterone values. Females receiving multiple matings had significantly greater releases of LH as measured by the area under the curve than those receiving single matings. There was significantly greater variability in the LH response of queens on Day 2 of oestrus compared to those on Day 4/5 for peak values and area under the curve; the only failure in release of LH was in queens on Day 2. Oestradiol levels did not differ significantly between Day 2 and Day 4/5 of oestrus. Progesterone values remained less than 1 ng/ml for 24 h after coitus. Both LH peak values and area under the curve were significantly greater for animals that became pregnant. There were also significant differences in coital behaviour between queens on Day 2 and those on Day 4/5 of oestrus.(ABSTRACT TRUNCATED AT 250 WORDS)     

慢性吗啡处理及戒断后大鼠杏仁核中Parvalbumin的表达变化

目的:观察慢性吗啡处理及戒断后大鼠杏仁核中Parvalbumin(PV)的表达变化,为其功能的研究提供形态学依据。方法:将30只健康雄性SD大鼠随机分为吗啡依赖组和生理盐水对照组。吗啡依赖组大鼠腹膜腔注射吗啡,2次/d,起始剂量为5 mg/kg,逐日递增5mg,至第10d为50mg/kg;对照组注射同体积的生理盐水。于末次注射后动物分别存活3h、3 d和14d。用免疫组化方法和相对平均灰度值检测杏仁核内PV的表达。结果:在生理盐水处理组各存活时间点,杏仁核内PV的表达相同。和生理盐水对照组相比,3h时杏仁核内PV的表达明显增加(P<0.05)。第3d时,杏仁核内PV的表达减少,明显低于第3 h组(P<0.05)。至第14d时,PV的表达又开始增加,明显高于第3 d组(P<0.05)。结论:本结果提示慢性吗啡处理及戒断后杏仁核PV的表达具有时相特异性;这种变化在戒断早期可能主要与躯体依赖相关,而戒断晚期主要与精神依赖相关。     

Effects of naloxone-precipitated withdrawal after a single dose of morphine on catecholamine concentrations in guinea-pig brain

The effect of naloxone-precipitated withdrawal after acute morphine was studied on the concentrations of noradrenaline (NA), 4-hydroxy-3-methoxyphenylethyleneglycol (MHPG), dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), and on the metabolite/parent amine ratios MHPG/NA, DOPAC/DA and HVA/DA, in eight regions of the guineapig brain. Guinea-pigs were treated with a single dose of morphine sulphate (15 mg/kg s.c.) or saline (control) and 2h later with naloxone hydrochloride (15 mg/kg s.c.) to precipitate withdrawal. The animals were decapitated at 0.5 h or 1 h after naloxone injections and their brains analysed for monoamine concentrations by HPLC-ECD. At 0.5 h after naloxone-precipitated withdrawal NA and MHPG levels, and the MHPG/NA ratio, were increased in the hypothalamus, and the NA levels were increased in the hypothalamus, medulla/pons and cortex 1 h after naloxone. Naloxoneprecipitated withdrawal also produced increased DA metabolism in the cortex, midbrain and medulla 0.5 h later, and in the cortex, hypothalamus and striatum 1 h later. Hence naloxone-precipitated withdrawal from acute morphine treatment produced a complex pattern of increased synthesis and metabolism of NA and DA which varied over time and with the brain region examined.     

Plasma prolactin levels in maturing intact and cryptorchid male rats: development of stress response.

In order to determine the possible role of the seminiferous tubules in the regulation of prolactin secretion during sexual development, male rats were rendered cryptorchid at 22 days of age, and thereafter different groups of animals were decapitated at 8-10 day intervals between Day 32 and Day 70. Cryptorchid rats showed destruction of the germinal epithelium accompanied by increased plasma FSH and, to a much lesser extent, increased plasma LH titers. Nevertheless, plasma prolactin levels were similar to those of intact controls throughout the entire period studied. Plasma prolactin titers in intact controls remained uniformly low from Day 20 to Day 70, contrasting with previous reports in which increasing prolactin levels have been observed during sexual development. To determine the reason for this apparent discrepancy, a longitudinal experiment was conducted in which intact and cryptorchid male rats were bled every 10 days from Day 30 to Day 70, following a 3-min period of exposure to ether fumes. The prolactin response to this stress increased markedly with age. A similar pattern of prolactin was observed in a cross-sectional study in which different groups of intact animals were bled following a 3-min period of ether exposure, at ages ranging from 20 to 70 daysmthe results indicate that unlike FSH secretion, prolactin secretion is not controlled by the seminiferous tubules. In addition, they suggest that the pattern of increasing plasma prolactin previously described in the developing male rat is at least in part caused by an age-dependent increase in responsiveness of prolactin to stress.     

Effect of morphine withdrawal on food and water intake, urine output and electrolyte excretion in the rat: participation of the renin-aldosterone-system in renal excretory changes

Male Wistar rats received two i.p. injections of morphine-HCl, 2.5 mg/kg at 8.00 a.m. and 2.00 p.m. on the 1st day: the dose was doubled every other day to reach a total daily dose of 40 mg/kg on the 4th day. This schedule was maintained for 12 days. On day 16 the animals received the last injection of morphine, 20 mg/kg. One hour later (9.00 a.m.) six rats were decapitated and PRA, PAC and ACTH were measured by radioimmunoassay. Groups of six rats were killed at 9.00 a.m. on the 1st, 2nd, 5th and the 8th day after morphine withdrawal. Control data for PRA, PAC and ACTH were obtained from eighteen saline-injected rats. Nine out of morphine-treated animals were kept in metabolism cages to investigate simultaneously food and water intake. and renal excretion. Morphine withdrawal after chronic morphine treatment in the rat resulted in antidiuresis and a reduction of electrolyte excretion which were not due to a reduction in water and food intake. The simultaneous increase of PRA and PAC associated with decreased electrolyte excretion indicates that, in addition to antidiuretic hormone, also the renin-aldosterone-system probably play a relevant role in the renal excretory changes after morphine withdrawal.     

Effect of pregnancy on oxytocin-induced release of prostaglandin F2 alpha in heifers

The effect of pregnancy on the release of prostaglandin F2 alpha (PGF2 alpha) in response to oxytocin (OT) has been examined. Fourteen cyclic heifers received one intravenous injection of 1 IU OT (n = 6) or 100 IU OT (n = 8) 17, 18, or 19 days (Day 17-19) after the onset of estrus (Day 0). Five of these animals also received 100 IU OT at Days 6 and 13 to determine the effect of OT at different times of the cycle. Frequent blood samples were taken for 60 min before and for 90 min after OT injection for the measurement of 15-keto-13,14-dihydro-PGF2 alpha (PGFM) by radioimmunoassay. The experiment was then repeated using the same animals at Day 17-19 of pregnancy (confirmed by the recovery of an embryo the day after OT injection). Following the injection of 1 IU OT, plasma PGFM reached its peak within 30 min with the increase significantly lower (P less than 0.05) in pregnant (1.13 +/- 0.10-fold) than in nonpregnant animals (2.07 +/- 0.27-fold). However, because only 3 of the 6 cyclic animals showed a response to 1 IU OT, the dose was increased to 100 IU in subsequent experiments. The animals that received 100 IU at Days 6 and 13 had no significant increase in PGFM concentrations (1.18 +/- 0.05-fold and 1.01 +/- 0.04-fold, respectively). At Day 17-19 the increase in plasma PGFM reached its peak 5-15 min after 100 IU OT and the increase was significantly greater in nonpregnant (3.23 +/- 0.17-fold) than in pregnant (1.21 +/- 0.02-fold; P = 0.003) heifers. Six of 11 animals injected at Day 17-19 of the cycle showed a decrease in progesterone (P4) the day after OT administration. These data show that the release of PGF2 alpha in response to OT is suppressed in pregnant animals in vivo, suggesting an antiluteolytic role for the embryo in luteostasis.     

Morphine dependence is associated with changes in neuropeptide S receptor expression and function in rat brain

Neuropeptide S (NPS) is a newly identified ligand for the previously discovered G-protein coupled receptor 154 now named NPSR. Recently, it has been found that NPSR gene expression is altered during ethanol withdrawal. In this study we tried to elucidate if NPSR gene expression is modified in response to morphine withdrawal and its protracted abstinence. To induce opioid dependence Wistar rats were treated for 7 days with morphine. Twelve hours and 7 days after the last morphine administration brains were removed and the expression of NPSR mRNA was analyzed by in situ hybridization (ISH). Successful induction of opioid dependence was confirmed by the naloxone-precipitated withdrawal test 2 h after the last morphine administration. Moreover, 7 days after the last morphine dose animals were checked for signs of anxiety and for intracerebroventricular (ICV) NPS (0.3 and 1.0 nmol) induced anxiolytic effects by elevated plus maze (EPM). Results showed that in morphine treated rats strong somatic signs of naloxone-precipitated withdrawal occurred. ISH data revealed changes in NPSR gene expression in the ventral tegmental area as well as in the basolateral amygdaloid and bed nucleus of stria terminalis at 12 h and 7 days into abstinence, respectively. At 7 days into abstinence post dependent animals showed higher levels of anxiety than controls which were significantly attenuated by NPS. These results demonstrated that morphine dependence induction led to (i) changes in NPSR mRNA expression; (ii) increased anxiety; and (iii) more potent anxiolytic-like effect of NPS.