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 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

As a part of a series of studies investigating the possible neurotoxicity of amitraz (AMZ), a formamidine pesticide, visual evoked potentials were recorded from Long-Evans rats following acute and short-term repeated exposures to AMZ. The first of three experiments examined the relationship between a single ip injection of AMZ (0, 50, and 100 mg/kg) and the latency and peak-to-peak amplitude of pattern-reversal (PREP) and flash-evoked potentials (FEP). The effects of another formamidine, chlordimeform (CDM; 40 mg/kg), were also studied for comparison purposes. Two hours after treatment, AMZ exposure produced large, dose-related increases in PREP amplitudes. Exposure to CDM produced similar changes. Neither compound changed FEP amplitudes. Body temperatures were reduced and evoked potential peak latencies were increased by both compounds. The latency increases were probably a secondary consequence of hypothermia. In the second experiment, PREPs were recorded before and 2, 24, 48, and 72 hr after treatment with AMZ (100 mg/kg). The time course of changes was biphasic in nature, with increases in amplitudes (N1P1, P1N2, and N2P3) 2 hr after treatment followed by subsequent depression in amplitude (P2N3) at 48 hr. Recovery occurred by 72 hr after treatment. The third experiment examined the effects of three daily treatments with either vehicle or 50 or 100 mg/kg AMZ. Body weights and body temperatures showed dose-related reductions which progressed with each additional treatment and recovered partially by 6 days after cessation of treatment. The PREPs of AMZ-treated rats agains showed biphasic changes, with N1P1 and P1N2 amplitudes significantly increased on each day of treatment and 1-2 days following the third treatment. Amplitude P2N3 showed an initial increase on the first 2 days of treatment, followed by subsequent, progressive amplitude reductions. In summary, AMZ produced two phases of change in visual evoked potentials. The first phase was characterized by large increases in PREP amplitudes without increasing FEP amplitudes in the same rats. The second phase was characterized by suppression of PREP P2N3 amplitude. Short-term repeated exposure produced signs of accumulating intoxication including progressive loss of body weight, lowered body temperature, and prolonged duration of evoked potential changes.
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PMID:Investigations of amitraz neurotoxicity in rats. II. Effects on visual evoked potentials. 304 May 1

Long-Evans hooded rats were exposed to single doses of toluene (PO) at 0, 250, 500 and 1000 mg/kg, to p-xylene (PO) at 0, 125, 250, 500, 1000 and 2000 mg/kg, and to inhalation of p-xylene for 4 hr at 0, 800 or 1600 ppm. The functional integrity of the visual system was evaluated using flash-evoked potentials (FEPs). The data indicated a significant depression in amplitude of FEP peak N3 at 250 mg/kg and higher dosages of toluene and p-xylene. A similar depression in peak N3 amplitude was observed following inhalation exposure to 1600 ppm p-xylene. The effects produced by oral administration of 500 mg/kg p-xylene or toluene lasted at least 8 hr, while the effect of inhaled p-xylene dissipated within 75 min of removal from the exposure. FEP peak N3 is presumed to be related to arousal, such that increases in arousal from a relaxed state should decrease amplitude. Rats administered amphetamine in dosages of 0.6, 1.2 and 2.5 mg/kg (known to increase arousal) also had reduced N3 amplitude. The effects of p-xylene and toluene on FEPs, while indicative of altered processing of visual information, may be secondary to changes in arousal or excitability.
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PMID:Acute exposures to p-xylene and toluene alter visual information processing. 339 23

We identified changes in hippocampal afterdischarge activity that follow administration of subcon vulsant doses (one-half the convulsant dose) of analeptic agents with known pharmacological action. Long-Evans rats (N = 104) with chronic bipolar electrodes implanted in the dorsal hippocampus, were injected i.p. with saline, caffeine (75 mg/kg), picrotoxin (2 mg/kg), or pentylenetatrazol (20 mg/kg) in 1 ml/kg volume 15 min before testing. Body temperature was measured at the beginning of the session to determine if significant change was associated with any of the treatments. Beginning at 10 microA, current (2-s train of 50-Hz biphasic pulses) was applied to hippocampal electrodes and intensity was increased in 10-microA steps until the afterdischarge sequence was elicited. Afterdischarge threshold, wet dog shake frequency, and the duration of the primary afterdischarge, the postprimary depression, and the rebound afterdischarge were measured. Caffeine administration produced a dramatic prolongation of the rebound afterdischarge, without affecting the duration of the primary afterdischarge. All other afterdischarge variables were unchanged by the caffeine treatment. Because caffeine blocks adenosine receptors at physiologic concentrations, adenosine action is implicated in the termination of the second, but not the first, spike train. Picrotoxin and pentylenetetrazol had no influence on the EEG, despite evidence of slight (1 degrees C) hypothermia. A decrease in wet dog shake frequency, however, was associated with picrotoxin administration. As picrotoxin and pentylenetetrazol are known gamma-aminobutyric acid (GABA) antagonists, the results suggest that GABA is involved minimally, if at all, in the hippocampal afterdischarge sequence.
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PMID:Differential effects of caffeine, picrotoxin, and pentylenetetrazol on hippocampal afterdischarge activity and wet dog shakes. 356 62

1. Extracellular recordings in pentobarbitone anaesthetized male Long-Evans rats examined the influence of electrical stimulation in the diagonal band of Broca on the excitability of 113 putative vasopressin-secreting and 22 putative oxytocin-secreting neurosecretory neurones in the hypothalamic supraoptic nucleus. 2. Single pulse or repetitive (5-20 Hz) stimulation in the ventral part of the diagonal band evoked a prominent reduction in the excitability of 83% of vasopressin-secreting neurones with no effect on the remainder. Amongst oxytocin-secreting neurones, 59% were unresponsive, 27% responded with an increase in activity while only 14% revealed an inhibitory pattern similar to vasopressin-secreting neurones. 3. Diagonal band stimulation-evoked inhibitions were reversibly abolished by local pressure applications of bicuculline methiodide (100 microM) to twenty out of twenty vasopressin secreting cells tested, whereas strychnine sulphate (100 microM) was without effect on four out of four cells tested. 4. In five out of five vasopressin-secreting cells tested, bicuculline applications reversibly abolished the reduction in their activity that follows peripheral baro-receptor activation. Failure to alter baroreflex-evoked depressions in firing during similar trials with prazosin hydrochloride (10 microM, six cells tested), timolol maleate (20 microM, six cells tested) or strychnine sulphate (100 microM, three cells tested) indicated the specificity of bicuculline's action. 5. These findings suggest that a GABAergic pathway from the diagonal band of Broca preferentially innervates vasopressin-secreting neurosecretory supraoptic nucleus (s.o.n.) neurones, and support the view that the baroreflex-induced depression in firing of s.o.n. vasopressin-secreting neurones is mediated in large part through this input.
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PMID:A gamma-aminobutyric-acid-mediated baroreceptor input to supraoptic vasopressin neurones in the rat. 362 45

Neuropathological and biochemical effects of neonatal exposure to the alkyl metal triethyltin were examined in juvenile male Long Evans rats. Rats were injected intraperitoneally on postnatal day 5 with 6 mg/kg of triethyltin bromide and sampled on day 20. The brains of tin-treated animals weighed significantly less than either saline or starved controls and exhibited a marked caviation of the ventrolateral surfaces. Histologically, neuronal necrosis was noted in the entorhinal and transitional cortex, an observation confirmed by immunocytochemical staining of astrocytes. Hippocampal involvement was further evidenced by a protrusion of the molecular layer of the dentate gyrus, and an abnormal histochemical staining pattern of acetylcholinesterase in this layer. Sections stained by the Timm's method for the deposition of heavy metals showed a marked reduction in the staining of the hippocampal CA4,3,2 sectors and an absence of stained laminae in the outer molecular layer of the dentate gyrus. Receptor binding assays indicated a selective depression of the benzodiazepine receptor in the hippocampus of tin-treated pups compared to starved controls. Taken in concert, these data indicate that neonatal exposure to triethyltin produces severe neuronal damage in the posterior cortex and a derangement of hippocampal afferent circuitry.
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PMID:Triethyltin-induced neuronal damage in neonatally exposed rats. 371 27

Newborn female Long-Evans rats were divided into groups of normal, hypothyroid [0.1% propylthiouracil (PTU) a reversible antithyroid goitrogen in the litter's drinking water], and hypothyroid rehabilitated (PTU water from birth to day 25, normal water thereafter). The rats were tested for several adaptive behavioral tasks between 40 and 90 days of age. At day 50, serum concentration of TSH and thyroid hormones revealed no detectable amounts of T4 and a 10-fold increase in TSH in the hypothyroid rats. At the same age in the rehabilitated animals, TSH levels were still below normal, a deficit fully normalized by day 90. Normal 50-day-old rats responded to pain stress (electric footshocks) by a significant depression of serum T4 and elevation of T3 levels within 10 min of treatment, whereas the rehabilitated animals exhibited an opposite pattern of response, i.e., an increase in the circulating T4 and a decrease in T3. At 50 days of age, both hypothyroid and rehabilitated rats showed decreased exploratory activity and no habituation in the hole-board test, whereas the locomotor activity of the rehabilitated females was significantly higher than that of the normals. No differences were found in the scores of passive avoidance learning (one trial step-through) among the three groups. Similarly, the rate of acquisition of the active one-way conditioned avoidance response (CAR) of the hypothyroid and rehabilitated rats did not differ significantly from that of the controls. However, the hypothyroid rats required significantly more unconditioned stimuli (footshocks) to acquire CAR and showed longer response latency and less intertrial responses. Although the hypothyroid rats showed no extinction of CAR, the rehabilitated rats were capable of extinction to an extent indistinguishable from normal rats. But compared with the normal animals, the rehabilitated rats showed significantly higher intertrial activity during both the acquisition and extinction phases of CAR.
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PMID:Exploratory behavior, learning ability, and thyroid hormonal responses to stress in female rats rehabilitating from postnatal hypothyroidism. 380 23

The effects of an acute fast on acetaminophen metabolism and hepatotoxicity were investigated in male Long Evans Hooded rats. Histologic studies confirmed that fasting potentiated acetaminophen-induced hepatic necrosis. The previous known fasting-induced decrease in hepatic levels of glutathione and depletion of glycogen levels were also confirmed. Pharmacokinetic studies revealed that, at high dose levels of acetaminophen, fasting decreased the overall rate of elimination as evidence by a longer blood half-life of the drug. The decreased clearance was largely the result of decreases in the apparent rate constants for glucuronidation (ca. 40%) and for sulfation (ca. 30%). Fasting had no significant effects on the apparent rate constants for formation of either acetaminophen mercapturate or the methylthio derivatives. The depression of the nontoxic glucuronidation and sulfation pathways resulted in an increased proportion of the dose converted to the toxic metabolite and, hence, contributed to the potentiation of liver injury in fasted rats. In addition, these studies demonstrated that significant glucuronidation capacity (ca. 60% of that in fed rats) was maintained in fasted rats, indicating that: the glucuronidation capacity was not directly correlated with glycogen levels; and in fasted rats the glucose required for UDP-glucuronic acid formation for acetaminophen glucuronidation was supplied from sources other than glycogen.
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PMID:Mechanisms of fasting-induced potentiation of acetaminophen hepatotoxicity in the rat. 382 34

Long-Evans rat pups were dosed orally from birth to 21 d with particulate Mn3O4 to obtain a daily dose of 0, 71, or 214 micrograms Mn/body weight . d. Assessments of the hypothalamic, pituitary, or testicular functions were determined by measuring the endogenous or stimulated serum concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and/or testosterone (T) at 21 or 28 d of age. Body, testes, and seminal vesicles weight and tissue concentrations of Mn were also evaluated. Only slight Mn treatment effects were seen in body and testes weights. No effects were seen either on unstimulated or stimulated FSH or LH serum concentrations. Although no Mn treatment effects were seen on endogenous or 2 h human chorionic gonadotropin (hCG) stimulate serum T concentrations, there was a reduction in the serum T following 7 d of hCG stimulation. The hypothalamic Mn concentrations in animals with these reproductive effects were three times those where alterations in the dopaminergic pathway have been reported. However, no indication of hypothalamic or pituitary malfunction was found. These results suggest that the site of Mn damage that causes depression of sustained serum T concentration is in the testicular Leydig cell.
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PMID:Assessment of the male reproductive system in the preweanling rat following Mn3O4 exposure. 392 53

A series of neurophysiological tests was performed on Long-Evans hooded rats treated with either 2-, 3-, or 4-methylpyridine at dosages of 100 mg/kg, approximately one-half the ip LD50. The tests contained measures of sensory function (paired pulse flash evoked potentials, pattern reversal evoked potentials, and brainstem auditory evoked responses) and cerebral excitability (pentylenetetrazol seizures and hippocampal afterdischarges). In general, rats treated with 2- and 3-methylpyridine were more affected than those treated with 4-methylpyridine. The changes observed were in many ways similar to those seen following administration of depressant compounds: increased latency of evoked potentials and increased latency to PTZ seizures. Not all findings, however, were consistent with previously observed patterns of central nervous system depression.
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PMID:Neurophysiological consequences of acute exposure to methylpyridines. 406 64

Effects of 2-ethoxyethanol (EE) on semen parameters in male rats were investigated employing an animal model that allowed assessment of toxicity and recovery in the same animal. Prior to exposure, 70-d-old Long-Evans hooded males were placed with ovariectomized, hormonally primed females on several occasions and their copulatory behaviors were monitored and scored. At 100 d of age, these males were mated with females that were sacrificed 15 min postejaculation. The semen sample was recovered from the female reproductive tract and scored for sperm motility, sperm count, and abnormal sperm morphology. Following this preexposure baseline assessment, the males were intubated with 0, 936, 1872, or 2808 mg EE/kg for 5 consecutive days. The males were mated weekly for the next 14 wk. Copulatory behaviors were monitored and ejaculated semen samples analyzed on wk 1, 4, 7, 10, and 14. The males were sacrificed at wk 16 and the testes and epididymides were processed for histological evaluation. Data analyses indicated that EE produced a rapid decline in sperm counts in the two highest groups, with most of the males becoming azoospermic by wk 7. The males in the low dose group also exhibited a significant decrease in sperm counts at this week. Additionally, there was a significant increase in abnormal sperm morphology at wk 7 in the low-dose males. Partial or complete recovery was apparent in the sperm parameters by wk 14, as evidenced by an increase in sperm counts and a decrease in abnormal morphology and further supported by epididymal and testicular histological assessment at wk 16. At sacrifice, there were no significant differences between groups on body weights, organ weights, or epididymal sperm counts, except for a significant depression of epididymal weight in the middle dose group. While high doses of EE produced a decline in sperm counts starting after the first week of exposure, the early spermatid-late spermatocyte stages, represented by mature spermatozoa in the wk 7 ejaculates, appeared to be particularly sensitive to this compound. Moreover, most of the males exhibited recovery following this acute dosing regimen.
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PMID:Male reproductive toxicity and recovery associated with acute ethoxyethanol exposure in rats. 649 98


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