Pulmonary injury in rats following continuous exposure to 60% O2 for 7 days

Morphological, biochemical, and physiological studies were done on rats exposed to 60% O2 for 7 days. This exposure did not induce O2 tolerance but instead caused a significant decrease in survival time of animals subsequently exposed to pure O2. The activity of lung superoxide dismutases and glucose-6-phosphate dehydrogenase were unchanged after exposure to 60% O2. A decrease in lung compliance was suggested by changes in the total lung capacity and in the pressure-volume curves of excised lungs. Ventilation of these animals with large tidal excursion resulted in pulmonary edema. Morphometric analyses revealed a significant decrease in alveolar air volume and an increase in the number of alveolar macrophages. The most significant lesions involved the pulmonary vascular bed. The volume and thickness of the capillary endothelium was decreased. There were focal areas of pericapillary fluid accumulations, and a number of the smaller vessels had perivascular edema. These findings suggest that significant pulmonary injury occurs in rats exposed to 60% O2 and that the primary site of injury is the pulmonary capillary endothelium.     

Neural and behavioral changes in rats following continuous exposure to an odor

Summary Continuous exposure of young rats to the almond-like odor of acetophenone or cyclohexanone for up to 4 months, resulted in distinct but similar patterns of degenerating mitral cells in their olfactory bulbs. Rats favored their exposure odor in olfactory preference tests (Fig. 2) and their acuity for it was not altered (Fig. 3). However, they appeared to exhibit a deficit in detecting a similar but novel odor. The results suggest that the remaining normal mitral cells in the bulbs of these animals are those stimulated by the exposure odor. Cells which show signs of degeneration (Fig. 4) may receive little or no input from the periphery. Controls exposed to a similar but non-odorous environment showed evidence of non-selective mitral cell degeneration. In addition they had a lower acuity for acetophenone and cyclohexanone than animals reared in a normal rat colony (Fig. 3). Anatomical and behavioral data from odor exposed and control groups, suggest that partial regeneration of altered mitral cells may have occurred during a 5 month period following exposure. Overall the results provide further evidence for a topographical projection of the olfactory receptor epithelium onto the olfactory bulb and spatial coding of different odors in the bulb.     

Effects of naloxone and naltrexone on receptive and proceptive behaviors in female rats.

The sexual receptive and proceptive behaviors induced by opiate antagonists, naloxone and naltrexone in estrogen-primed ovariectomized rats were observed under the presence of sexually active males. The females were treated intraperitoneally with naloxone or naltrexone at doses ranging from 0.5 to 4.0 mg/kg and the sexual behavior of females was tested before and after the injection of drug. The results obtained suggest that the opiate antagonists play a role in the regulation of lordosis behavior, but not proceptive behavior in female rats.     

Translation of muscle mRNA in rats following acute exposure to Pb2+ or Cd2+

The hindleg muscle of rats was studied 2 days following the i.p. administration of 0.5 mg Pb2+ /100 g body wt or 0.12 mg Cd2+ /100 g body wt or both Pb2+ and Cd2+. The incorporation of [14C]leucine into proteins was measured using mRNA obtained from the muscle polysomes. The translatability of this poly(A)+ RNA in a mRNA-dependent reticulocyte lysate was elevated similarly in each of the preparations from heavy metal treated rats compared to control rats. Evidence for increased mRNA activity for glyceraldehyde-3-phosphate dehydrogenase and actin was obtained.     

Analeptic and antianaleptic effects of naloxone and naltrexone in rabbits.

Naloxone (5 mg/kg), but not naltrexone, shortened the duration of anaesthesia in rabbits pretreated with pentobarbital. This analeptic effect was blocked by atropine, but not by methylatropine; it thus appears that a central cholinergic mechanism is involved. In contrast, smaller doses of both naloxone and naltrexone attenuated the arousal property of thyrotropin releasing hormone (TRH). Naloxone, but not naltrexone, also antagonized the analeptic property of d-amphetamine. In conscious animals naloxone potentiated, whereas naltrexone attenuated, the excitatory effects of TRH and d-amphetamine.     

Narcotic antagonist activity of several metabolites of naloxone and naltrexone tested in morphine dependent mice (38558).

A rabbit liver enzyme system was used to produce the 6beta-OH reduced metabolites of naloxone and naltrexone. GC analysis indicated the presence of some 6alpha-OH metabolite in these samples. The narcotic antagonist activity of these 6beta-OH metabolite samples were compared to naloxone, naltrexone and standard 6alpha-OH naltrexone (EN-2260A) using the jumping response of morphine pellet implanted mice. For the naloxone series, the potencies were: Naloxone greater than EN 2265A greater than 6 beta-OH maloxone. For the naltrexone series: Naltrexone greater than EN 2260A greater than beta-OH naltrexone. The low potency of the reduced metabolites the rapid onset of action of the parent compounds militate against the formation of these metabolites contributing substantially to the overall narcotic antagonist action of the parent compounds.     

Early exposure to naloxone increases blood pressure in normotensive and hypertensive rats

Continuous $\text{in}\text{utero}$ and postpartum exposure of SH and WKY rats to naloxone results in a significant increase in their systolic blood pressure relative to respective control animals. After six weeks of age, however, naloxone was no longer effective in sustaining this increase in blood pressure. Chronic exposure to naloxone beginning at three weeks of age failed to produce any significant differences in blood pressure between treated and control animals. Although naloxone has been shown to elevate blood pressure in hypotensive states, this report represents the first example of an increase produced by the narcotic antagonist in the normotensive state.     

Prevention of continuous light-induced anovulation in rats by early exposure to continuous light

Continuous illumination (LL) beginning at 22 days of age caused precocious puberty followed by persistent estrus with anovulation in female offspring originating from mother rats exposed to a 14L:10D light-dark cycle prior to and during pregnancy. However, LL had no deleterious effect on reproductive cycles of offspring reared in LL and originating from mothers exposed to LL prior to and during pregnancy. These rats had a normal onset of puberty in LL, a normal 4-day estrous cycle, a periodic rise of plasma estrogen prior to the periodic appearance of the preovulatory luteinizing hormone (LH) surge, and spontaneous ovulation in LL continued until at least 300 days of age. Also, the female offspring of these rats showed a similar resistance to the deleterious effects of LL on cyclic ovulation. These results support the following interpretation: 1) offspring from mother rats exposed to LL prior to and during pregnancy become insensitive to the deleterious effects of LL on cyclic ovulation, 2) neural elements controlling cyclic release of LH are not totally photoperiod (14L:10D)-dependent, and 3) in the absence of daily 14L:10D signals, an endogenous clock, possibly timed by daily laboratory signals (temperature, noise, taking of vaginal smears), may provide time cues for cyclic LH release.     

Tolerance to morphine in the rat: its prevention by naloxone.

Development of tolerance after a single injection of morphine in the Wistar-Lewis rat can be estimated by the attenuation of the response to a second injection of morphine given three days later. If naloxone is given 35 minutes after the first morphine injection and after the appearance of measurable analgesia, attenuation of the effects of the second morphine injection is not seen. It appears that naloxone blocks the development of tolerance to morphine even if given after the morphine-receptor interaction responsible for analgesia has been initiated. The temporal relationship between the prior injection of morphine and the subsequent administration of naloxone is being explored.     

ACTH and corticosterone response to naloxone and morphine in normal, hypophysectomized and dexamethasone-treated rats

The effect of opiate receptors blocker naloxone on ACTH and corticosterone secretion in normal, dexamethasone-treated and hypophysectomized rats was studied. A dose-related increase in plasma corticosterone level was found at 45 min after s.c. injection of naloxone in a dose range of 0.25-2.0 mg kg-1. The rise in plasma corticosterone was preceded by a slight increase in plasma ACTH. Acute morphine administration in a relatively low dose (6 mg kg-1 s.c.) induced a significant rise in both plasma ACTH and corticosterone levels. Dexamethasone treatment was followed by low basal corticosterone level, by total inhibition of the stress response and response to morphine injection, while the response to ACTH administration was normal. Under these circumstances as well as in rats 6 days after hypophysectomy, naloxone failed to increase plasma corticosterone levels. It is concluded that a direct stimulation of corticosteroid biosynthesis in adrenal cortex is not involved in the mechanism of naloxone-induced activation of pituitary-adrenocortical function.     

Effects of morphine and naloxone on pain sensitivity after radiation injuries in rats

Radiation in doses 150 Gy induces different changes in pain sensitivity in rats by thermal (analgesia) and electrical (hyperalgesia) stimuli. Naloxone (0.1 and 1 mg/kg) and morphine (5 mg/kg) show, that analgesia is realized due to opioid mechanisms.     

Acupuncture analgesia in rats and its changes under the effect of morphine and naloxone

It was established in chronic experiments on rats that electric acupuncture of the acupuncture point noticeably decreases pain reaction to electric stimulation of the tail. Morphine given in a subanalgetic dose (5 mg/kg) potentiated acupuncture analgesia, while 5 mg/kg of naloxone completely abolished it. Potential mechanisms of analgesia realization during electric acupuncture are discussed.     

Testicular function of rats following exposure to microwave radiation

Male Sprague-Dawley rats were exposed for 6 h per day for nine days to pulse-modulated microwave radiation (1.3 GHz, at 1-microseconds pulse width, 600 pulses per second). Exposures were carried out in cylindrical waveguide sections at a mean dose rate of 6.3 mW/g; sham controls were treated similarly and received no irradiation. At time periods corresponding to 0.5, 1.0, 2.0, and 4.0 cycles of the seminiferous epithelium, groups of four sham-irradiated and four irradiated rats were killed and the testes removed for analysis. Net mass of the testes, epididymides, and seminal vesicles; daily sperm production (DSP) per testis and per gram of testis; sperm morphology; and the number of epididymal sperm were determined. There were no statistically significant differences between the sham-irradiated and irradiated groups with respect to any measured variable. In a group of seven surrogate animals of similar body mass, the dose rate of 6.3 mW/g caused a net change in body temperature (via rectal probe) of 1.5 degrees C.     

Effects of naloxone and acetylcholine on medial thalamic and cortical units in naive and morphine dependent rats.

The administration of 0.5 mg of testosterone propionate (TP) for 3 days to castrated male rats caused ³H-leucine incorporation into pineal proteins to increase significantly by 79%. TP effects depended on time of administration; rats receiving TP at 06.00 h exhibited a significant 150% increase in pineal protein synthesis 24 h later whereas rats injected at 14.00 h only showed a 54% increase in ³H-leucine incorporation into proteins. Superior cervical ganglionectomy decreased pineal testosterone uptake $\text{in vitro}$ by 21% and pineal protein synthesis by 27%; in addition it blocked the stimulatory effects of TP on protein synthesis. Ganglionectomy also modified the $\text{in vitro}$ metabolism of testosterone by pineal cells; it increased the amounts of ³H-androstenedione and decreased ³H-5∝-androstanedione extracted from pineal glands incubated with ³H-testosterone. These results indicate that the sympathetic nervous input reaching the pineal via the superior cervical ganglia is important to modulate the early steps of androgen action on the pinealocytes.     

Neonatal behavioral toxicity in rats following prenatal exposure to methanol

Although methanol (MEOH) may assume a significant role as a fuel, which implies wide availability, little is known of its toxicity apart from acute poisoning episodes in human adults. Even less is known about its toxicity in developing organisms. This experiment studied the early behavioral development of rats whose mothers had consumed MEOH during gestation by measuring the responses of suckling (postnatal day 1) and nest-seeking (postnatal day 10). Primigravida Long-Evans rats were divided into three groups (N = 10). Two of the groups consumed drinking solutions of 2% MEOH instead of distilled water either on gestational days 15-17 (MEOH 1) or 17-19 (MEOH 2). No maternal toxicity was apparent as measured by weight gain, gestational duration, and daily fluid intake. Daily MEOH consumption averaged 2.5 gm/kg over the 3-day period in both MEOH groups. Litter size, birth weight, and infant mortality did not differ among the three groups. Postnatal growth and date of eye opening were unaffected. MEOH pups required longer than controls to begin suckling on postnatal day 1. On postnatal day 10, they required more time to locate nesting material from their home cages. These data suggest that prenatal MEOH exposure induces behavioral abnormalities early in life that are unaccompanied by overt toxicity.     

Maternal behavior after the administration of morphine or naloxone to pregnant female rats and the pain sensitivity and brain mu-opioid receptors in the progeny]

Morphine or naloxone injected twice a day (10 mg/kg/day) to rat females from 15 to 18 days of gestation had no effect on their litter size or body weight of pups. Time necessary for the female to bring pups into the nest from the opposite end of the cage, that is a characteristic of maternal care and negatively correlated with the mean body weight of the pup in the litter, did not change after treatment with drugs during gestation. Newborns treated with mu-opioid receptor ligands during intrauterine development had an elevated number of 3H-naloxone binding sites in the brain. However, the number of 3H-naloxone binding sites on the 9 and 16 days of life, as well as pain thresholds under electric stimulation of the tail at a month age were equal in these rats and offsprings of the intact or saline treated mothers.     

Neuroendocrine responses to cocaine do not exhibit sensitization following repeated cocaine exposure.

Cocaine-induced enhancement of motor activity and extracellular dopamine concentrations exhibits sensitization upon repeated exposure. In this study, the neuroendocrine responses to cocaine were examined following cocaine pretreatment regimens which have been shown to produce behavioral sensitization. Adult male rats were injected with cocaine (15 mg/kg, IP) once daily for 14 days, followed by a dose-response challenge with cocaine (1-15 mg/kg, IP) either 18 hours or 7 days after the final pretreatment injection. Blood was collected 15 minutes following injections for radioimmunoassay of ACTH, corticosterone, prolactin, and renin. Cocaine increased plasma ACTH and corticosterone, while it decreased prolactin and renin concentrations. Pretreatment with cocaine for 2 weeks did not alter any of these endocrine responses after either the 18 hour or 7 day interval between pretreatment and challenge injections. In contrast, sensitization to the locomotor stimulant effects of cocaine was observed on the final day of pretreatment injections, and 7 days later. These data suggest that these endocrine effects of cocaine do not exhibit sensitization following repeated cocaine exposure.     

Increments in glucose, glucagon and insulin after morphine in rats, and naloxone blocking of this effect.

In awake rats adapted to experimental conditions and allowed food ad libitum, hyperglycemia was induced by the administration of morphine 10 mg/kg through indwelling catheters in the external jugular vein. High glucose values were measured at 5, 15 and 25 min. Glucagon values were high at 5 and 15 min, and again at basal level at 25 min. Insulin was increased after morphine both at 5, 15 and 25 min, whereas somatostatin levels did not change after morphine. When morphine was administered together with naloxone after an initial 10 min period of naloxone administration, there was no increment in glucose, insulin or somatostatin values; neither at 5, 15 or 25 min. There was a remarkable glucagon decrease after naloxone and morphine remaining from 5 to 25 min. Then, one of the possible mechanisms for the hyperglycemic response after morphine may be an opioid effect on pancreas, stimulating glucagon and thereby causing hepatic glucose output.