Impact of escitalopram on nocturnal sleep, day-time sleepiness and performance compared to amitriptyline: a randomized, double-blind, placebo-controlled study in healthy male subjects.

INTRODUCTION: Antidepressant drugs vary in their effects on sleep, day-time sedation and performance. Up to now, no data are available for either escitalopram (ESCIT) or amitriptyline (AMI), measuring these by an objective test, such as the MULTIPLE SLEEP LATENCY TEST (MSLT). SUBJECTS AND METHODS: We therefore investigated the impact of a single evening dose of 10 mg ESCIT on polysomnographically recorded nocturnal sleep, day-time sleepiness and performance in comparison to 75 mg AMI and placebo (PLAC) in healthy male subjects. RESULTS: Both antidepressants significantly suppressed REM sleep (p<0.001). Although polysomnographically measured sleep continuity was impaired after ESCIT (p=0.006), subjective estimates of sleep parameters did not differ. Periodic limb movements (PLMS) were increased after AMI (p<0.001) but not after ESCIT. Processing speed and performance were enhanced after ESCIT compared with AMI (p=0.011), but not with PLAC. Next-day alertness was significantly impaired by AMI (p=0.012), but not by ESCIT. Mean day-time sleep onset latencies increased significantly after evening ESCIT (p<0.001). In contrast, AMI led to a pronounced increase of day-time sleepiness (p=0.007). DISCUSSION: This study demonstrates that single evening doses of either AMI or ESCIT exhibit different effects on next-day vigilance and alertness in terms of a slightly stimulating effect of ESCIT and a significant reduction after AMI.

[Disturbances of slow-wave sleep and psychiatric disorders]. / Störungen des Tiefschlafs und psychische Erkrankungen.

Slow-wave sleep is defined as sleep stages 3 and 4 that characteristically show slow delta EEG activity during polysomnography. The percentage of slow-wave sleep normally declines with age. Sleep disorders are a common symptom of many psychiatric disorders. In polysomnographic recordings they mostly manifest as disturbances of sleep continuity. In some disorders changes in REM sleep are also found. A reduction of slow-wave sleep has most often been described in patients with depression and addictive disorders. More recent research implicates slow-wave sleep as an important factor in memory consolidation, especially the contents of declarative memory. Psychotropic drugs influence sleep in different ways. Hypnotic substances can reduce the deep sleep stages (e.g. benzodiazepines), whereas 5-HT2C antagonists increase the percentage of slow-wave sleep. Whether a selective impairment/alteration of slow-wave sleep is clinically relevant has not yet been proved.

Performance of broiler chickens fed diets supplemented with a direct-fed microbial.

From hatch to 18 d of age broilers were fed starter diets with (0.9 kg/ton) or without direct fed microbial (DFM). At 18 d, birds were weighed and, within DFM treatment (trt), randomly assigned to battery pens. In Exp 1, a 2 x 2 factorial arrangement of nutrient density [control (C, 19.3% protein (CP), 0.84%, Ca 0.37% nonphytin P (nPP); and 17.1% CP, 0.8% Ca, and 0.3% nPP in the grower (Gr) and finisher (Fn) diets, respectively) and moderate (M) (17% CP, 0.69% Ca, 0.30% nPP; 15% CP, 0.66% Ca, 0.25% nPP in the Gr and Fn diets, respectively)] and DFM concentration [0 or 0.9 kg/ton (++)] was used. Exp 2 was a 2 (DSM at 0 and 0.45 kg/ton) x 3 (nutrient densities) factorial. Exp 2 included a low (L) nutrient density that differed from diet M only in Ca and nPP concentrations and an added trt, diet M with 0.45 kg/ ton DFM as in Exp 1. At the end of the Gr and Fn weight, feed efficiency, apparent nutrient retention were determined, and 4 birds per pen were sampled for tibia ash. In Exp 2, gains in the Gr phase were 1,122.0, 983.7, 1,121.5, 930.7, and 1,151.5 g in birds fed the C, M, M+, L, and L+ diets, respectively. Addition of DFM to the M diet overcame the negative effect of nutrient concentration on performance but not when the L diet was fed. Nutrient level and DFM affected apparent protein, Ca, and P retention at 32 or 42 d of age with retention increasing as nutrient level decreased and with DFM added to the diet. Ca and P retention at 28 d (Exp 1) was higher in birds fed M++ (45.8 and 46%, respectively) than in those fed the C diet (38.7 and 40.0%, respectively). Feeding the M and L diets resulted in lower tibia ash than that of birds fed the C diet, but the addition of DFM to low nutrient diets overcame this negative effect.

Enhanced mucosal immunity against Eimeria acervulina in broilers fed a Lactobacillus-based probiotic.

The effect of feeding a Lactobacillus-based probiotic on intestinal intraepithelial lymphocyte (IEL) subpopulations and subsequent protection against coccidiosis was investigated in broiler chickens. Day-old male broilers were fed standard rations without control (CONT) or with a commercial probiotic (PROB) Primalac. Differences in IEL subpopulations were assessed by flow cytometry at 21 d postprobiotic treatment. At 25 d of age, a group of randomly selected birds from each diet was inoculated orally with 10,000 (per bird) sporulated oocysts of Eimeria acervulina and kept on the same diets. Fecal material, sera, and intestinal washes were collected 10 d postchallenge with E. acervulina. Birds on the PROB diet had more IEL expressing the surface markers CD3, CD4, CD8, and alphabetaTCR than those of the CONT diet. The probiotic-fed chickens produced less oocysts (P < 0.0001) compared to the untreated, control group (368 x 10(6) in CONT vs. 89 x 10(6) in PROB). The interferon-gamma levels in both serum and intestinal secretions were not significantly different between the two groups. However, CONT group showed higher antibody levels against a recombinant coccidial antigen in the intestinal secretions than the PROB group. No significant difference was found in serum antibody levels against the same antigen. These results dearly indicate that the probiotic bacteria impacted the local immune response as characterized by altered IEL subpopulations and increased the birds' resistance to E. acervulina as reflected by reduced oocyst shedding.

Effect of vitamin A deficiency on host intestinal immune response to Eimeria acervulina in broiler chickens.

The effects of vitamin A (VitA) deficiency on the host intestinal immune response and disease susceptibility to coccidiosis were investigated in broiler chickens following oral infection with Eimeria acervulina (EA). Day-old male broilers were fed milo-soybean meal diets either with 8,000 IU VitA/kg feed (CONT) or without added VitA (A-DEF). At 25 d, a group of randomly selected birds from each treatment was inoculated orally with EA-sporulated oocysts. Intestinal immune response was assessed by the changes in the duodenum intraepithelial lymphocyte (IEL) subpopulations using flow cytometry at 35 d in in fected and noninfected birds. Concanavalin A (ConA)-induced spleen lymphocyte proliferation was tested using dimethylthiazol diphenyltetrazolium bromide colorimetric assay. Whether challenged or not with EA, A-DEF birds had fewer IEL expressing the surface markers CD3, CD4, CD8, alphabetaTCR, and gammabetaTCR. Without EA challenge, A-DEF birds had more surface IgA-expressing cells than CONT birds. Upon challenge, A-DEF chickens showed lower CD4+ IEL than CONT chickens. Following EA infection, CD8+ IEL increased in the CONT group, whereas no change was found in CD8+ IEL of A-DEF birds. A higher number of EA oocysts was recovered from A-DEF birds than from CONT birds (9.2 x 10(8) vs 5.4 x 10(8), respectively; P < or = 0.05). Serum samples taken 10 d post challenge showed higher antibody level against a recombinant coccidial antigen in A-DEF birds than in CONT birds. The A-DEF birds showed depressed ConA-induced lymphoproliferation response and produced lower serum interferon-gamma than CONT birds. These data show that VitA deficiency compromised local immune defenses of challenged birds, as reflected in lymphocyte profiles, oocyst shedding, and interferon-gamma levels in A-DEF birds.

Human ARX gene: genomic characterization and expression.

Arx is a homeobox-containing gene with a high degree of sequence similarity between mouse and zebrafish. Arx is expressed in the forebrain and floor plate of the developing central nervous systems of these vertebrates and in the presumptive cortex of fetal mice. Our goal was to identify genes in Xp22.1-p21.3 involved in human neuronal development. Our in silico search for candidate genes noted that annotation of a human Xp22 PAC (RPCI1-258N20) sequence (GenBank Accession No. AC002504) identified putative exons consistent with an Arx homologue in Xp22. Northern blot analysis showed that a 3.3kb human ARX transcript was expressed at high levels in fetal brain. A 5.9kb transcript was expressed in adult heart, skeletal muscle, and liver with very faint expression in other adult tissues, including brain. In situ hybridization of ARX in human fetal brain sections at various developmental stages showed the highest expression in neuronal precursors in the germinal matrix of the ganglionic eminence and in the ventricular zone of the telencephalon. Expression was also observed in the hippocampus, cingulate, subventricular zone, cortical plate, caudate nucleus, and putamen. The expression pattern suggests that ARX is involved in the differentiation and maintenance of specific neuronal cell types in the human central nervous system. We also mapped the murine Arx gene to the mouse genome using a mouse/hamster radiation hybrid panel and showed that Arx and ARX are orthologues. Therefore, investigations in model vertebrates may provide insight into the role of ARX in development. The recent identification of ARX mutations in patients with various forms of mental retardation make such studies in model organisms even more compelling.

The initiation of smooth pursuit eye movements and saccades in normal subjects and in "express-saccade makers".

A vast knowledge exists about saccadic reaction times (RT) and their bi- or multimodal distributions with very fast (express) and regular RT. Recently, there has been some evidence that the smooth pursuit system may show a similar RT behavior. Since moving targets usually evoke a combined pursuit/saccade response, we asked which processes influence the initiation of pursuit and saccadic eye movements. Furthermore, we investigated whether and how the pursuit and saccadic system interact during the initiation of eye movements to moving targets. We measured the RT of the initial smooth pursuit (iSP) response and of the first corrective saccade and compared the RT behavior of both. Furthermore we compared the behavior of the corrective saccades to moving targets to that of saccades to stationary targets, known from the literature. The stimulus consisted of a target that moved suddenly at constant velocity (ramp). In addition, prior to the movement, a temporal gap, a position step or a combination of both could occur (gap-ramp, step-ramp, gap-step-ramp, respectively). Differently from most previous studies, we chose step and ramp with the same direction to provoke competition between the pursuit and saccade system. For the first time we investigated pursuit initiation in "express-saccade makers" (ES makers), a subject group known to produce an abnormally high percentage of short-latency saccades in saccade tasks. We compared their results with subject groups who were either naive or trained with respect to saccade tasks. The iSP started at approximately 100 ms, which corresponds to express saccade latencies. These short iSP-RT occurred reflex-like and almost independent of the experimental task. A bimodal frequency distribution of RT with a second peak of longer iSP-RT occurred exclusively in the ramp paradigm. The RT of the first corrective saccades in a pursuit task were comparable with that in a saccade task and depended on the stimulus. The ability of ES makers to produce a high number of express saccades was transferred to corrective saccades in the pursuit task, but not to pursuit initiation. In summary, short-latency pursuit responses differ from express saccades with respect to their independence of experiment and subject group. Therefore, a simple analogy to express saccades cannot be drawn, although some mechanisms seem to act similarly on both the pursuit and the saccade system (such as disengagement of attention with the gap effect). Furthermore, we found evidence that the initial pursuit response and the first corrective saccade are processed independently of each other. The first corrective saccades to moving targets behave like saccades to stationary targets. Normal pursuit but abnormal saccade RT of ES makers can be explained by recent theories of superior colliculus (SC) function in terms of retinal error handling.

CmC(A/T)GG DNA methylation in mature B cell lymphoma gene silencing.

DNA methylation has been linked to gene silencing in cancer. Primary effusion lymphoma (PEL) and myeloma are lymphoid malignancies that arise from terminally differentiated B cells. Interestingly, PEL do not express immunoglobulins or most B lineage-specific genes. The B cell-specific B29 (Igbeta/CD79b) gene is silenced in PEL and some myelomas but is expressed in other normal and malignant B cells. B29 expression was reactivated in PEL by demethylating and histone deacetylase inhibiting treatments. Bisulfite sequencing revealed two types of DNA methylation in silenced B29 promoters: at conventional CpG and at CC(A/T)GG B29 promoter sites. The pattern of methylated CpG ((m)CpG) and C(m)C(A/T)GG B29 promoter methylation observed was similar to that recently reported for epigenetic silencing of an integrated retrovirus. Methylation of C(m)C(A/T)GG sites in the B29 promoter significantly repressed in vivo transcriptional activity. Also, methylation of a central conserved C(m)CTGG B29 promoter site blocked the binding of early B cell factor. This methylated motif formed DNA-protein complexes with nuclear extracts from all cell types examined. Therefore, C(m)C(A/T)GG methylation may represent an important type of epigenetic marker on mammalian DNA that impacts transcription by altering DNA-protein complex formation.

Ingested bovine amniotic fluid enhances morphine antinociception in rats.

Ingestion by rats of rat placenta or amniotic fluid enhances opioid-mediated, or partly opioid-mediated, antinociception produced by morphine injection, vaginal or cervical stimulation, late pregnancy, and foot shock. This phenomenon is believed to be produced by a placental opioid-enhancing factor (POEF). Ingestion by rats of human or dolphin placenta has also been shown to enhance opioid antinociception, suggesting that POEF may be common to many mammalian species. We tested bovine amniotic fluid (BAF) for its capacity to enhance morphine antinociception in female Long-Evans rats, as determined by percentage change from baseline tail-flick latency in response to radiant heat, and we report that 0.50 mL BAF effectively enhanced morphine antinociception but did not by itself produce antinociception. The efficacy of POEF across species suggests that POEF may have been functionally (and structurally) conserved during evolution. Furthermore, the availability of POEF at parturition, as well as its ability to enhance pregnancy-mediated antinociception without disrupting maternal behavior, offers a tenable explanation for the long-debated ultimate causality of placentophagia.

The effectiveness of benzimidazole derivatives for the treatment and prevention of histomonosis (blackhead) in turkeys.

The benzimidazole derivatives, albendazole and fenbendazole were evaluated for their effectiveness in the treatment and prevention of histomonosis (blackhead) in turkeys. Histomonosis was produced in 5 week-old birds by placing them on broiler breeder litter known to be contaminated with Heterakis gallinae ova and the protozoan Histomonas meleagridis. In the first trial, at the onset of confirmed clinical disease, birds were treated orally with metronidazole, a compound known to be effective against Histomonas. Those receiving metronidazole had significantly greater mean body weight gains during the treatment period and the 2 weeks following treatment than untreated controls. Treated birds also had significantly lower caecal and liver lesion scores. These findings served to validate the method of disease reproduction and establish its suitability for testing the benzimidazoles. Similar trials were conducted to determine the therapeutic value of albendazole at 100.0 mg/kg of body weight and fenbendazole at 10.0 mg/kg body weight, administered orally twice a day for 5 consecutive days. Under these conditions, both drugs were found to be ineffective as treatments. A final trial was conducted to assess the prophylactic value of albendazole and fenbendazole administration. At the time of placement on contaminated litter, birds were medicated as previously described with the exception that treatment was continued for 14 consecutive days, the approximate incubation period for histomonosis. The trial was terminated on the 16th day. In the case of both albendazole and fenbendazole, treatment was associated with a significant increase in mean body weight gain and lower caecal and liver lesion scores. It is believed that the observed prophylactic effect may be attributed to the destruction of the transport vector e.g., Heterakis larvae, or to direct killing of the flagellated form of Histomonas which is normally found in the caecal lumen and is considered to be more sensitive to chemotherapeutic agents than the amoeboid form found in tissues.

Species difference in the ovarian toxicity of 1,3-butadiene epoxides in B6C3F1 mice and Sprague-Dawley rats.

1,3-Butadiene (BD) is an ovarian carcinogen in mice, but not in rats. Since species variation in metabolism of BD has been associated with the greater sensitivity of mice to BD-induced carcinogenicity, the extent of biotransformation and detoxification of BD and its epoxides may play a critical role in other ovotoxic effects of this compound. Thus, the ovotoxic potency of the BD epoxides was determined. Butadiene monoepoxide (BMO, 0.005-1.43 mmol/kg b.w.), butadiene diepoxide (BDE, 0.002-0.29 mmol/kg b.w.), or vehicle was administered i.p. to female B6C3F1 mice and Sprague-Dawley rats for 30 days. Following day 30, tissues were removed and weighed, and the number of pre-antral ovarian follicles counted. BMO was ovotoxic in mice as demonstrated by decreases in reproductive organ weights (1.43 mmol/kg b.w.) and follicular counts, but not in rats at any dose tested. In mice the ED50 values for BMO for small and growing follicles were 0.29 and 0.40 mmol/kg b.w., respectively. BDE was ovotoxic in both species, however mice were more sensitive to BDE than rats. Ovarian and uterine weights were decreased in mice at 0.14 and 0.29 mmol/kg b.w. of BDE treatment, and in rats at 0.29 mmol/kg b.w. only. The ED50 values for BDE in mice were 0.10 and 0.14 mmol/kg b.w. for small and growing follicles, respectively, ED50 values could not be determined in rats since only 32% of the follicular population was depleted at the highest concentration tested. Thus, BMO and BDE exhibited a greater ovotoxic potential in mice, as compared to rats. In addition, in each species the diepoxide was the most potent ovotoxicant.

Ovarian toxicity of 4-vinylcyclohexene and related olefins in B6C3F1 mice: role of diepoxides.

4-Vinylcyclohexene (VCH) is an ovarian toxicant in mice. Studies have established that bioactivation of VCH to epoxides is required for its ovotoxicity, with vinylcyclohexene diepoxide being the most potent epoxide of VCH in terms of follicular depletion. To determine the role of the diepoxide in the ovarian toxicity of VCH and related compounds, a structure-activity study was conducted. Following administration (ip) of VCH for 30 days, a significant depletion of ovarian follicles was observed. No alteration of small ovarian follicle counts occurred following treatment with structural analogues of VCH (vinylcyclohexane, ethylcyclohexene, and cyclohexene) that contain only a single unsaturated site. These VCH analogues were converted to monoepoxides both in vitro and in vivo. In addition, when the monoepoxide forms of the VCH analogues were administered to mice, they were not ovotoxic. These results indicate that vinylcyclohexene diepoxide may be the ultimate ovotoxic metabolite of VCH. A diepoxide was also shown to be critical for butadiene- and isoprene-induced follicular loss. Butadiene monoepoxide, butadiene diepoxide, and isoprene were ovotoxic. In contrast, the monoepoxide, epoxybutane, was not ovotoxic. The ovotoxicity of these compounds correlated with their chemical reactivity as assessed by alkylation of nicotinamide. Vinylcyclohexene diepoxide and butadiene diepoxide had a 3.5- to 10-fold higher chemical reactivity as compared to their monoepoxide precursors and structurally related monoepoxides. Thus, a relationship exists between chemical reactivity and ovotoxicity. Only those compounds which are metabolized to a diepoxide or are a diepoxide were ovotoxic. The formation of these diepoxide metabolites may in turn be linked to the ovarian toxicity and carcinogenicity of these olefins.

Destruction of preantral follicles in adult rats by 4-vinyl-1-cyclohexene diepoxide.

4-vinyl-1-cyclohexene diepoxide (VCD) is known to destroy oocytes in ovaries of immature rats. Since ovaries functionally differ between immature and adult animals, we examined the effect of VCD on oocytes in adult rats. Adult (58 days) and immature (28 days) rats were injected daily (30 days) with vehicle or VCD. Each group contained 10 rats. During this time, cyclicity was determined daily by vaginal cytology. Animals were terminated on day 31 and tissues were collected. Oocytes were counted; livers, spleens, and uteri were weighed. VCD reduced the number of regular estrous cycles/30 days in adults, but not immature rats (n = 20, P < 0.05). VCD reduced the number of oocytes in adult and immature rats (n = 20, P < 0.05). Liver, spleen, or ovarian weights were not affected by VCD in either group. VCD reduced uterine weight in adult (n = 20, P < 0.05) but not in immature rats. These results demonstrate that VCD decreases uterine weight in adult rats and as with immature rats, selectively destroys oocytes in ovaries of adults.

Effectiveness of different types of clay for reducing the detrimental effects of aflatoxin-contaminated diets on performance and serum profiles of weanling pigs.

Three trials were conducted with recently weaned pigs (n = 198) to determine the effects of feeding different types of clay in conjunction with aflatoxin-contaminated diets. In Trial 1, pigs (n = 54; trial length 4 wk) were assigned to either an uncontaminated treatment (NC), 800 ppb of aflatoxin from contaminated corn (AC), or AC with one of four clays. In Trial 2 (n = 81; trial length 5 wk), pigs were assigned to NC, AC (500 ppb of aflatoxin from rice starch), or AC with one of seven types of clay. In both trials, pigs fed AC had decreased ADG and gain:feed ratios (P < .05) compared with controls. The clays differed in their ability to produce gains similar to those of controls. The clays did reduce changes in the serum measurements normally affected by aflatoxin, including albumin, total protein, gamma glutamyltransferase (GGT), and alkaline phosphatase (ALP) levels, in a manner similar to their effect on ADG. In Trial 3, pigs (n = 63) were assigned to one of seven diets for 4 wk: NC, AC (800 ppb of aflatoxin) with no clay, AC with one of four levels of a treated Ca bentonite (.25, .5, 1, and 2%), or AC and .5% hydrated sodium calcium aluminosilicate. The addition of treated Ca bentonite to AC improved ADG (P < .05) and ADFI (P < .01) linearly. Gain:feed ratios were not affected by treatments. The inclusion of treated Ca bentonite to the AC diet linearly decreased aspartate aminotransferase (AST) levels and quadratically decreased ALP and GGT levels (P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Seizures induced by the cocaine metabolite benzoylecgonine in rats.

The half-life (t1/2) of cocaine is relatively short, but some of the consequences of its use, such as seizures and strokes, can occur hours after exposure. This led us to hypothesize that a metabolite of cocaine may be responsible for some of those delayed sequelae. We evaluated the potential of the major metabolite of cocaine, benzoylecgonine (BE), to cause seizures. Two separate equimolar doses (0.2 and 0.4 mumol) of either cocaine or BE were injected ventricularly in unanesthetized juvenile rats. Treated rats were then evaluated for incidence, latency, and seizure pattern or for locomotor activity in animals without seizures. BE-Induced seizures occurred more frequently and had significantly longer latencies than those induced by equimolar amounts of cocaine. Whereas cocaine-induced seizures were best characterized as brief, generalized, and tonic and resulted in death, those induced by BE were prolonged, often multiple and mixed in type, and rarely resulted in death. Electrical recordings from the hippocampus showed a rhythmic progression in EEG frequency and voltage with clinical seizure expression. BE-Injected rats that did not have seizures had significantly more locomotor activity than cocaine-injected animals without seizures. The finding that cocaine- and BE-induced seizures differ in several respects suggests more than one mechanism for cocaine-induced seizures and emphasizes the importance of a cocaine metabolite, BE.

Effects of benzoylecgonine on the behavior of suckling rats: a preliminary report.

A major metabolite of cocaine, benzoylecgonine, causes behavioral activation that progresses to seizures when given intraventricularly to 2-week-old rats. The seizures are characterized by running, hopping, and vocalizing and are mixed with shorter-duration tonic episodes. Pretreatment with haloperidol, at a dose aimed at blocking stereotyped behavior, did not suppress these behaviors. In contrast, seizures were prevented by antiepileptic drugs, with the order of potency being diazepam greater than phenobarbital greater than phenytoin. We hypothesize that the long-lasting cocaine metabolite, benzoylecgonine, contributes to the infant cocaine intoxication syndrome.

Placental opioid-enhancing factor (POEF): generalizability of effects.

A substance in amniotic fluid and placenta (POEF for Placental Opioid-Enhancing Factor) has been shown to enhance opiate- or opioid-mediated analgesia in rats. Recent studies have only touched on the generalizability of the phenomenon. The present studies further tested the generalizability of the POEF effect: they examined sex specificity of the mechanism; whether POEF activity exists in afterbirth material of species other than the rat; whether POEF activity exists in tissue other than afterbirth material; whether POEF activity could be demonstrated after injection rather than ingestion of afterbirth material; and whether POEF enhances all opioid-mediated phenomena. We found that (a) POEF is effective in male rats as well as in female rats; (b) POEF activity exists in human and dolphin afterbirth material; (c) ingestion of pregnant-rat liver does not produce enhancement of opioid-mediated analgesia; (d) POEF does not seem to be effective when amniotic fluid is injected either IP or SC; and (e) POEF does not modify morphine-induced hyperthermia.

Amniotic-fluid ingestion enhances morphine analgesia during morphine tolerance and withdrawal in rats.

Ingestion of placenta and amniotic fluid has been shown to enhance opioid-mediated analgesia in rats produced by morphine injection, footshock, vaginal/cervical stimulation, and during late pregnancy. The present study was designed to investigate the effects of amniotic fluid ingestion on the characteristics of morphine dependency and withdrawal. Tail-flick latencies in Long-Evans rats were determined before and after repeated daily injections of morphine sulfate. It was found that ingestion of amniotic fluid after establishment of the morphine dependency, coupled with an injection of an otherwise ineffective dose of morphine, enhanced analgesia in morphine-dependent rats, and reversed hyperalgesia seen during withdrawal from morphine dependency.

Amniotic fluid ingestion before vaginal/cervical stimulation produces a dose-dependent enhancement of analgesia and blocks pseudopregnancy.

A substance in amniotic fluid (AF) and placenta has been shown to enhance analgesia produced by morphine, late pregnancy, footshock, and vaginal/cervical stimulation (VS). When morphine-induced analgesia was assessed previously, the degree of enhancement by ingestion of AF or placenta was found to be a function of the amount of analgesia being generated. We have extended these results to include the analgesia produced by VS. Analgesia induced by 75, 125, 175, or 225 g of vaginal/cervical pressure was measured in rats pretreated with 0.25 ml (by orogastric infusion) of either AF or saline. AF infusion enhanced the analgesia produced by 125 g VS, but did not affect the analgesia produced by 75, 175, or 225 g VS. Unexpectedly, we also found that infusion of AF shortly before the application of VS prevents VS-induced pseudopregnancy (PsP). Whereas the incidence of PsP following 75, 125, or 175 g VS was less than 19% and not statistically different for AF and saline pretreatments, the incidence of PsP after 225 g VS was 44% in saline-pretreated rats, but only 10% in AF-pretreated rats. Protection from the induction of pseudopregnancy, which could be caused by mechanical stimulation of the cervical area during delivery, may be an additional benefit of parturitional ingestion of placenta and amniotic fluid (placentophagia).