Role of ethanol metabolism in the inhibition of testosterone biosynthesis in rats in vivo: importance of gonadotropin stimulation

The mechanisms by which ethanol (EtOH, 1.5 g/kg) inhibits testicular testosterone synthesis were studied in nonstimulated and human chorionic gonadotropin (hCG, 50 IU/kg)-treated male rats. To dissociate the effects caused by ethanol metabolism, the alcohol dehydrogenase inhibitor 4-methylpyrazole (4MP, 10 mg/kg) was given to half of the rats 30 min before EtOH. The 4MP had little or no effect in the nonstimulated rats on the EtOH-induced decreases in the concentrations of serum testosterone and of the intratesticular steroids of the testosterone biosynthetic pathway measured, but reduced the EtOH-induced elevation in the intratesticular pregnenolone-to-progesterone ratio. In contrast, 4MP pretreatment markedly reversed the EtOH-induced decrease in serum and intratesticular testosterone and increase in intratesticular pregnenolone concentrations in the hCG-stimulated rats. Simultaneously, the EtOH-induced elevations in the intratesticular pregnenolone/progesterone and androstenedione/testosterone ratios were abolished. In the EtOH-treated rats whose EtOH metabolism was blocked by 4MP pretreatment, the intratesticular testosterone concentrations were negatively correlated with the elevated serum corticosterone levels. It is concluded that: (1) EtOH metabolism is involved in the inhibition of testicular steroidogenesis in vivo. This effect is pronounced during gonadotropin-stimulated conditions. Thus, previously reported "discrepancies" between the in vivo and in vitro results are clarified; (2) corticosterone seems also to be involved in the EtOH-induced inhibition of steroidogenesis. This effect is also pronounced during gonadotropin-stimulated conditions; and (3) without external gonadotropin stimulation other inhibitory mechanisms, such as decreased stimulation by luteinizing hormone, are prevalent.     

Ethanol-induced hypothermia and ethanol consumption in the rat are affected by low-level microwave irradiation

Microwave irradiation of rats by circularly polarized, 2,450-MHz, pulsed waves (2-μs pulses; 500 pps) was performed in waveguides to determine effects on ethanol-induced hypothermia and on ethanol consumption. Rats injected intraperitoneally with ethanol (3 g/kg in a 25% v/v water solution) immediately after 45 min of microwave irradiation exhibited attenuation of the initial rate of fall in body temperature, which was elicited by the ethanol, but exhibited no significant difference in maximal hypothermia as compared with that of sham-irradiated rats. Microwave irradiation did not affect the consumption of a 10% sucrose (w/v) solution by water-deprived rats. However, it enhanced the consumption of a solution of 10% sucrose (w/v) + 15% ethanol (v/v) by water-deprived animals. These results were obtained at a specific absorption rate (SAR) of 0.6 W/kg, which rate of energy dosing would require a power density of 3–6 mW/cm² if exposure of the animals had occurred to a 12-cm plane wave.     

Ethanol-induced increased endogenous homocysteine levels and decreased ratios of SAM/SAH are only partially attenuated by exogenous glycine in developing chick brains

The effects of exogenous ethanol (EtOH) and/or glycine on chick (Gallus gallus) embryo viability, brain apoptosis (caspase-3 activities), and the endogenous levels of brain homocysteine (HoCys), S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH), and SAM/SAH were studied. Embryonic EtOH exposure caused decreased embryo viability as measured by EtOH-induced reductions in % living embryos at theoretical stage 37, EtOH-induced reductions in embryo masses, and EtOH-induced reductions in brain caspase-3 (Casp-3) activities. Exogenous glycine failed to attenuate EtOH-induced decreased embryo viability and EtOH-induced increased brain Casp-3 activities. Embryonic EtOH exposure caused elevated levels of endogenous HoCys, decreased levels of SAM, increased levels of SAH, and decreased SAM/SAH ratios in embryonic chick brains. While exogenous glycine failed to attenuate EtOH-induced increased HoCys levels, exogenous glycine attenuated EtOH-induced decreased levels of SAM, increased levels of SAH, and decreased SAM/SAH levels in embryonic chick brains.     

Effects of maternal strain on ethanol responses in reciprocal F1 C57BL/6J and DBA/2J hybrid mice

Variations in maternal behavior, either occurring naturally or in response to experimental manipulations, have been shown to exert long-lasting consequences on offspring behavior and physiology. Despite previous research examining the effects of developmental manipulations on drug-related phenotypes, few studies have specifically investigated the influence of strain-based differences in maternal behavior on drug responses in mice. The current experiments used reciprocal F1 hybrids of two inbred mouse strains (i.e. DBA/2J and C57BL/6J) that differ in both ethanol (EtOH) responses and maternal behavior to assess the effects of maternal environment on EtOH-related phenotypes. Male and female DBA/2J and C57BL/6J mice and their reciprocal F1 hybrids reared by either DBA/2J or C57BL/6J dams were tested in adulthood for EtOH intake (choice, forced), EtOH-induced hypothermia, EtOH-induced activity and EtOH-induced conditioned place preference (CPP). C57BL/6J and DBA/2J mice showed differences on all EtOH responses. Consistent with previous reports that maternal strain can influence EtOH intake, F1 hybrids reared by C57BL/6J dams consumed more EtOH during forced exposure than did F1 hybrids reared by DBA/2J dams. Maternal strain also influenced EtOH-induced hypothermic responses in F1 hybrids, producing differences in hybrid mice that paralleled those of the inbred strains. In contrast, maternal strain did not influence EtOH-induced activity or CPP in hybrid mice. The current findings indicate that maternal environment may contribute to variance in EtOH-induced hypothermia and EtOH intake, although effects on EtOH intake appear to be dependent upon the type of EtOH exposure.     

Alcohol enhances characteristic releases of dopamine and serotonin in the central nucleus of the amygdala

The amygdaloid complex (AMY) is implicated in emotional and motivational aspects of behavior, including the formation of positive reinforcement association. AMY may also associated with brain rewarding circuitry. In the present study, the effect of ethanol (EtOH) on the release of dopamine (DA) and serotonin (5-HT) was studied in the central amygdaloid nucleus (CeAMY), and projecting excitatory afferents to the ventral tegmental area (VTA), of freely moving Wistar rats by brain microdialysis. Within 20 min of i.p. injection of EtOH (2 g/kg), the levels of DA and 5-HT in the CeAMY dialysate increased over the baseline value by 270 and 160% (N = 6-7), respectively. Addition of EtOH (25, 50 and 100 mM) to the microdialysis perfusion medium for 1 h caused a 115-150% dose-related increase in the extracellular level of DA in the CeAMY. 100 mM EtOH-induced CeAMY DA release continued to increase for 1 h after the perfusion medium was returned to normal perfusion medium. In contrast, the CeAMY 5-HT level was increased only by the addition of 100 mM EtOH for 1 h to 130% for 80 min. The stimulation of the CeAMY by EtOH through the microdialysis membrane showed delayed responses of DA and 5-HT compared with the i.p. injection of EtOH. Overall, the present findings are not sufficient to conclude whether EtOH acts directly or indirectly on the major monoamine nerve cells in the CeAMY, but the degree of acute EtOH action affected the differences in time at the peak response on EtOH-induced DA and 5-HT releases in the CeAMY via VTA.     

Dorsal noradrenergic bundle lesions fail to alter opiate withdrawal or suppression of opiate withdrawal by clonidine

Previous work has shown that clonidine effectively supresses many of the signs of opiate withdrawal. The present study was designed to test the hypothesis that the supression of opiate withdrawal by clonidine is mediated by forebrain noradrenergic projections of the locus coeruleus. Two groups of 24 rats each were subjected to either a 6-hydroxydopamine lesion of the dorsal noradrenergic bundle (Lesion group) or a sham, vehicle injection (Sham group). All rats were made dependent on morphine by subcutaneous implantation of one 75 mg silastic morphine pellet for three days followed by 3 more days with two additional 75 mg pellets. Following removal of the morphine pellet, withdrawal was precipitated in all rats by subcutaneous injection of 4 mg/kg of naloxone. Pretreatment 10 min. before withdrawal with clonidine (0.1 or 0.2 mg/kg) produced a significant attenuation of withdrawal signs as compared to saline injected rats; this effect was equally significant in both sham and lesion groups. Lesions of the locus coeruleus had no effect on withdrawal, nor did they affect the ameliorating action of clonidine. These results substantiate the observation that clonidine can effectively attenuate signs of opiate withdrawal in the rat, but fail to support the hypothesis that these effects are mediated by the forebrain projections of the locus coeruleus.     

Estrogen and gender do not affect fatigue resistance of extensor digitorum longus muscle in rats.

The effects of estrogen on skeletal muscle fatigue are controversial. To determine the effects of estrogen and gender on rat extensor digitorum longus (EDL) muscle, we either injected 40 microg beta-estradiol 3/benzoate.kg BW(-1) to female rats or sham injected male or female rats for 14 days. Subsequently a 90 min fatigue protocol consisting of electrical stimulation at 10 Hz delivered in 500 ms trains was administered. Force was recorded for a 5 s period at the start of the protocol (0 min) and at 5 min intervals until completion following 90 min of stimulation. After 90 min, EDL force generation at 10 Hz stimulation declined in all groups to between 50-60 % of initial values. However, no significant difference in fatigue rate or final 10 Hz stimulated force was seen between females administered estrogen, sham injected females or males. Hence, estrogen administration and gender did not significantly affect EDL muscle fatigue in this model.     

Effects of dopaminergic and serotonergic drugs on ethanol-induced hypothermia

The effects of dopaminergic and serotonergic drugs on ethanol-induced hypothermia were studied in the rat. Pretreatment with haloperidol attenuated the hypothermia in a dose-dependent manner. Apomorphine produced a dose-dependent effect on the hypothermia. At a dose of 2.0 mg/kg, apomorphine potentiated ethanol-induced hypothermia, whereas at 0.1 mg/kg, it produced a delayed attenuation effect between 30 min and 45 min after its injection. The former effect was blocked by haloperidol, whereas the latter was not affected by haloperidol, but blocked by pretreatment with parachlorophenylalanine. It is concluded that both dopamine and serotonin exert modulatory effects on ethanol-induced hypothermia.     

The influence of age on radiation-induced cognitive deficit:experimental studies on brain irradiation of 30 gy in 10 sessions and 12 hours in the Wistar rat at 1 1/2, 4 and 18 months age

The objective of this study was to determine the influence of age on the learning and memory dysfunction induced by cranial radiation in the male Wistar rat. Ninety-six 45-day-old, 70 4-month-old, and 78 18-month-old male rats were divided in two equal groups: (i) irradiated and (ii) control. A course of whole-brain radiation therapy (30 Gy in 10 fractions over 12 days) was administered to the irradiated group, while the control group received sham irradiation. Sequential behavioral studies including one and two-way avoidance tests were undertaken before and after the 7 months following radiation. The results suggest that radiation induced progressive and irreversible memory dysfunction in elderly (18-month-old) rats, but this effect was partial or almost reversible in the 4-month-old and 45-day-old rats, respectively. In return, the learning dysfunction was age non-dependent despite the fact that is occurs more rapidly in the young (45 days, 4 months) rats.     

Pentagastrin-induced gastric acid secretion in the diabetic rats: role of insulin

Streptozotocin-induced diabetic rats have excessively pentagastrin-simulated acid output in which insulin seems to attenuate rather than further stimulate acid output. The aim of this study was to determine the insulin impact on pentagastrin-stimulated acid output of diabetic and non-diabetic rats to resolve whether an attenuated effect does exist. Diabetic rats were induced by the streptozotocin i.v. injection four days before acid study. Some streptozotocin-treated rats additionally received daily insulin (2.4 IU/kg) injection. Using an autotitrator, acid output was measured every five minutes by the titration of gastric perfusate. Basal output was collected for 45 min before the 90-min pentagastrin infusion (0.89 microg/kg/min). Plasma gastric inhibitory polypeptide (GIP) levels were measured. Both doses (0.067 and 0.133 IU/kg/min) of insulin infusion resulted in stimulated acid output in normal rats. The subsequent insulin infusion (0.133 IU/kg/min) for non-diabetic rats undergoing pentagastrin-treatment suppressed their stimulated acid output almost down to the basal level. Pentagastrin-stimulation led to the excessively increased acid output of diabetic rats throughout the whole infusion period (P < 0.01). Correction of hyperglycemia with insulin for diabetic rats normalized the stimulated acid output. Measured basal and stimulated plasma GIP levels of those diabetic rats during acid stimulation remained higher, regardless of insulin treatment (P < 0.05). Our results suggest that insulin has the ability to attenuate pentagastrin-stimulated acid output in rats, whereas GIP is not involved in this attenuation. This effect appears to be responsible for the excessive acid output of diabetic rats undergoing pentagastrin stimulation.     

Reduced de novo synthesis of 5-methyltetrahydrofolate and reduced taurine levels in ethanol-treated chick brains

In previous studies, exogenous ethanol (3 mmol EtOH/kg egg) caused a 1.6-fold increase in chick brain homocysteine (HoCys) levels at 11 days of development and the mixture of 3 mmol EtOH/kg egg and 34 μmol folic acid/kg egg attenuated EtOH-induced increases in chick brain HoCys levels. Because HoCys is converted to methionine utilizing the methyl donor, 5-methyltetrahydrofolate (5-methyl THF), we studied whether exogenous ethanol (3 mmol EtOH/kg egg) or the mixture of 3 mmol EtOH/kg egg and 34 μmol 5-methyl THF/kg egg inhibited chick brain 10-formyltetrahydrofolate dehydrogenase (10-FTHF DH; EC 1.5.1.6) activities and brain N⁵, N¹⁰-methylenetetrahydrofolate reductase (MTHFR; EC 1.5.1.20) activities at 11 days of development. Three daily dosages of 3 mmol EtOH/kg egg (E_0–2) caused approximately a 7-fold reduction in brain 10-FTHF DH activities and approximately a 1.9-fold reduction in brain MTHFR activities as compared to controls at 11 days of development (p ≤ 0.05). Because HoCys is also removed by the transsulfuration pathway, which synthesizes taurine, we studied whether exogenous ethanol (3 mmol EtOH/kg egg) or the mixture of 3 mmol EtOH/kg egg and 34 μmol 5-methyl THF/kg egg influenced chick brain taurine levels. In EtOH-treated and EtOH and 5-methyl THF-treated embryos, brain taurine levels decreased by approximately 5.5-fold and 6.2-fold as compared to controls, respectively (p ≤ 0.05). Exogenous 5-methyl THF failed to attenuate EtOH-induced decreased brain taurine levels at 11 days of development.     

Alcohol impairs insulin and IGF-I stimulation of S6K1 but not 4E-BP1 in skeletal muscle

The present study determined whether acute alcohol (ethanol; EtOH) intoxication in rats impaired components of the insulin- and IGF-I-signaling pathway in skeletal muscle. Rats were administered EtOH, and 2.5 h thereafter either insulin, IGF-I, or saline was injected and the gastrocnemius removed. EtOH did not alter the total amount or tyrosine phosphorylation of the insulin receptor, IGF-I receptor, insulin receptor substrate (IRS)-1, or protein kinase B (PKB)/Akt under basal or hormone-stimulated conditions. In contrast, the ability of insulin or IGF-I to phosphorylate T389 and T421/S424 on S6K-1 was markedly diminished by EtOH, and these changes were associated with a reduction in the phosphorylation of the ribosomal protein S6. Under basal conditions, EtOH altered the distribution of eukaryotic initiation factor (eIF)4E, as evidenced by a decreased amount of active eIF4E. eIF4G complex, an increased amount of inactive eIF4E. 4E-binding protein (BP)1 complex, and decreased 4E-BP1 phosphorylation. In contrast, EtOH did not impair the ability of either hormone to reverse the changes in eIF4E distribution or 4E-BP1 phosphorylation. Pretreatment with a glucocorticoid receptor antagonist was unable to attenuate either the basal EtOH-induced changes in eIF4E distribution or the impaired ability of IGF-I to stimulate S6K1 and S6 phosphorylation. Hence, acute alcohol intoxication alters selected aspects of translational control under both basal and anabolic hormone-stimulated conditions in skeletal muscle in a glucocorticoid-independent manner.     

Quantitative magnetic resonance spectroscopy reveals a potential relationship between radiation-induced changes in rat brain metabolites and cognitive impairment

To test the efficacy of magnetic resonance spectroscopy (MRS) in identifying radiation-induced brain injury, adult male Fischer 344 rats received fractionated whole-brain irradiation (40 or 45 Gy given in 5-Gy fractions twice a week for 4 or 4.5 weeks, respectively); control rats received sham irradiation. Twelve and 52 weeks after whole-brain irradiation, rats were subjected to high-resolution MRI and proton MRS. No apparent lesions or changes in T(1)- or T(2)-weighted images were noted at either time. This is in agreement with no gross changes being found in histological sections from rats 50 weeks postirradiation. Analysis of the MR spectra obtained 12 weeks after fractionated whole-brain irradiation also failed to show any significant differences (P > 0.1) in the concentration of brain metabolites between the whole-brain-irradiated and sham-irradiated rats. In contrast, analysis of the MR spectra obtained 52 weeks postirradiation revealed significant differences between the irradiated and sham-irradiated rats in the concentrations of several brain metabolites, including increases in the NAA/tCr (P < 0.005) and Glx/tCr (P < 0.001) ratios and a decrease in the mI/tCr ratio (P < 0.01). Although the cognitive function of these rats measured by the object recognition test was not significantly different (P > 0.1) between the irradiated and sham-irradiated rats at 14 weeks postirradiation, it was significantly different (P < 0.02) at 54 weeks postirradiation. These findings suggest that MRS may be a sensitive, noninvasive tool to detect changes in radiation-induced brain metabolites that may be associated with the radiation-induced cognitive impairments observed after prolonged fractionated whole-brain irradiation.     

Psychoactive-drug response is affected by acute low-level microwave irradiation

The effects of various psychoactive drugs were studied in rats exposed for 45 min in a circularly polarized, pulsed microwave field (2450 MHz; SAR 0.6 W/kg; 2-microseconds pulses, 500 pps). Apomorphine-induced hypothermia and stereotypy were enhanced by irradiation. Amphetamine-induced hyperthermia was attenuated while stereotypy was unaffected. Morphine-induced catalepsy and lethality were enhanced by irradiation at certain dosages of the drug. Since these drugs have different modes of action on central neural mechanisms and the effects of microwaves depend on the particular drug studied, these results show the complex nature of the effect of microwave irradiation on brain functions.     

Attenuated febrile response to lipopolysaccharide in rats with biliary obstruction

Patients with biliary tract obstruction have unexplained, inordinately high rates of perioperative morbidity and mortality, whereas cholestatic animals display abnormal hypothalamic responses to pyrogenic stimuli. We asked if obstructive cholestasis was associated with abnormal fever generation. Male Sprague-Dawley rats (250 g) underwent laparotomy for implantation of thermistors and either bile duct resection (BDR) or sham operation. After recovery, temperatures were recorded by telemetry and conscious, unrestrained rats in each group were injected intraperitoneally with either interleukin-1beta (IL-1beta;1 microg/kg) or Escherichia coli lipopolysaccharide (LPS; 50 microg/kg). Baseline temperatures in both groups were similar. Febrile responses after IL-1beta injection in BDR and sham groups were not significantly different. However, in response to LPS injection, BDR rats showed an initial hypothermia with a subsequently attenuated febrile response. Administration of anti-tumor necrosis factor-alpha (TNF-alpha) antibody 2 h before LPS injection blocked the LPS-induced hypothermia seen in BDR animals. However, serum levels of TNF-alpha were not significantly different between sham and BDR animals after LPS injection at any time point measured (0, 1.5, and 3 h).     

Quantitative trait loci for sensitivity to ethanol intoxication in a C57BL/6J?×?129S1/SvImJ inbred mouse cross

Individual variation in sensitivity to acute ethanol (EtOH) challenge is associated with alcohol drinking and is a predictor of alcohol abuse. Previous studies have shown that the C57BL/6J (B6) and 129S1/SvImJ (S1) inbred mouse strains differ in responses on certain measures of acute EtOH intoxication. To gain insight into genetic factors contributing to these differences, we performed quantitative trait locus (QTL) analysis of measures of EtOH-induced ataxia (accelerating rotarod), hypothermia, and loss of righting reflex (LORR) duration in a B6×S1 F2 population. We confirmed that S1 showed greater EtOH-induced hypothermia (specifically at a high dose) and longer LORR compared to B6. QTL analysis revealed several additive and interacting loci for various phenotypes, as well as examples of genotype interactions with sex. QTLs for different EtOH phenotypes were largely non-overlapping, suggesting separable genetic influences on these behaviors. The most compelling main-effect QTLs were for hypothermia on chromosome 16 and for LORR on chromosomes 4 and 6. Several QTLs overlapped with loci repeatedly linked to EtOH drinking in previous mouse studies. The architecture of the traits we examined was complex but clearly amenable to dissection in future studies. Using integrative genomics strategies, plausible functional and positional candidates may be found. Uncovering candidate genes associated with variation in these phenotypes in this population could ultimately shed light on genetic factors underlying sensitivity to EtOH intoxication and risk for alcoholism in humans.     

Alcohol impairs leucine-mediated phosphorylation of 4E-BP1, S6K1, eIF4G,and mTOR in skeletal muscle

Acute alcohol (EtOH) intoxication impairs skeletal muscle protein synthesis. Although this impairment is not associated with a decrease in the total plasma amino acid concentration, EtOH may blunt the anabolic response to amino acids. To examine this hypothesis, rats were administered EtOH or saline (Sal) and 2.5 h thereafter were orally administered either leucine (Leu) or Sal. The gastrocnemius was removed 20 min later to assess protein synthesis and signaling components important in translational control of protein synthesis. Oral Leu increased muscle protein synthesis by the same magnitude in Sal- and EtOH-treated rats. However, the increase in the latter group was insufficient to overcome the suppressive effect of EtOH, and the rate of synthesis remained lower than that observed in rats from the Sal-Sal group. Leu markedly increased phosphorylation of Thr residues 36, 47, and 70 on 4E-binding protein (BP)1 in muscle from rats not receiving EtOH, and this response was associated with a redistribution of eukaryotic initiation factor (eIF) 4E from the inactive eIF4E. 4E-BP1 to the active eIF4E. eIF4G complex. In EtOH-treated rats, the Leu-induced phosphorylation of 4E-BP1 and changes in eIF4E availability were partially abrogated. EtOH also prevented the Leu-induced increase in phosphorylation of eIF4G, the serine/threonine protein kinase S6K1, and the ribosomal protein S6. Moreover, EtOH attenuated the Leu-induced phosphorylation of the mammalian target of rapamycin (mTOR). The ability of EtOH to blunt the anabolic effects of Leu could not be attributed to differences in the plasma concentrations of insulin, insulin-like growth factor I, or Leu. Finally, although EtOH increased the plasma corticosterone concentration, inhibition of glucocorticoid action by RU-486 was unable to prevent EtOH-induced defects in the ability of Leu to stimulate 4E-BP1, S6K1, and mTOR phosphorylation. Hence, ethanol produces a leucine resistance in skeletal muscle, as evidenced by the impaired phosphorylation of 4E-BP1, eIF4G, S6K1, and mTOR, that is independent of elevations in endogenous glucocorticoids.     

Prior pregastric food stimulation and gastrin-releasing peptide1-27 (GRP) synergize to inhibit sham feeding.

The hypothesis that prior pregastric food stimulation is sufficient to reveal an inhibitory effect of gastrin-releasing peptide1-27 (GRP) on sham feeding was tested in 11 male rats equipped with chronic gastric cannulas. Rats were sham fed a high-carbohydrate solution during a 45-min test session, after 17-h food deprivation. GRP (16 or 32 microg/kg) or saline was injected intraperitoneally either at the onset or 5 or 15 min after the onset of sham feeding. This allowed for a 0-, 5-, or 15-min period of pregastric food stimulation before GRP or saline injections. Sham intake was recorded every 5 min, and behavior was observed every minute. GRP inhibited sham feeding when it was administered after 5 or 15 min of prior pregastric food stimulation, but not when it was administered at test onset. A nonsignificant increase in resting behavior and decrease in feeding behavior were associated with the decrease in sham feeding. No anomalous behaviors were noted. We conclude that a synergy between GRP and prior pregastric, presumably oral, food stimulation is sufficient to inhibit sham feeding.     

Alpha-tocopherol and gamma-tocopherol attenuate ethanol-induced changes in membrane fatty acid composition in embryonic chick brains

BACKGROUND: This project investigated whether or not EtOH-induced reductions in the levels of long-chain polyunsaturated membrane fatty acids could be attenuated by exogenous exposure to either alpha-tocopherol, gamma-tocopherol, or diallyl sulfide (DAS). METHODS: At 0 days of development, fertile chicken eggs were injected with a single dose of either saline supplemented with various concentrations of EtOH, alpha- or gamma-tocopherol and EtOH, or DAS and EtOH. At 18 days of development, brains were isolated and subjected to membrane analyses. RESULTS: When exposed to EtOH, concentrations ranging from 0-60.50 microm/Kg egg, dose-dependent decreases in the levels of brain 18:0, 18:1 (n-9), 18:2 (n-6), 18:3 (n-3), and 20:4 (n-6) were observed. These ethanol-induced changes in membrane fatty acid composition correlated with ethanol-induced reductions in brain mass, brain protein levels, acetylcholine esterase (AChE) activities and correlated with increased lipid hydroperoxide levels. Exposure to either 2.5 microm alpha-tocopherol/Kg egg and 6.050 mm EtOH/Kg egg, or 2.5 microm alpha-tocopherol/ Kg egg and 6.050 mm EtOH/Kg egg attenuated EtOH-induced changes in membrane fatty acid composition, brain mass, brain protein levels, AChE activities, and lipid hydroperoxide levels. Embryonic exposure to the cytochrome p450-2E1 inhibitor, diallyl sulfide (DAS), also attenuated EtOH-induced decreases in long-chain, unsaturated membrane fatty acids. However, embryonic exposure to DAS promoted abnormally low brain mass. CONCLUSION: EtOH-induced reductions in the levels of brain long-chain polyunsaturated fatty acid are caused by lipid peroxidation.     

Effects of acute low-level microwaves on pentobarbital-induced hypothermia depend on exposure orientation

Two series of experiments were performed to study the effects of acute exposure (45 min) to 2,450-MHz circularly polarized, pulsed microwaves [1 mW/cm², 2-μs pulses, 500 pps, specific absorption rate (SAR) 0.6 W/kg] on the actions of pentobarbital in the rat. In the first experiment, rats were irradiated with microwaves and then immediately injected with pentobarbital. Microwave exposure did not significantly affect the extent of the pentobarbital-induced fall in colonic temperature. However, the rate of recovery from the hypothermia was significantly slower in the microwave-irradiated rats and they also took a significantly longer time to regain their righting reflex. In a second experiment, rats were first anesthetized with pentobarbital and then exposed to microwaves with their heads either pointing toward the source of microwaves (anterior exposure) or pointing away (posterior exposure). Microwave radiation significantly retarded the pentobarbital-induced fall in colonic temperature regardless of the orientation of exposure. However, the recovery from hypothermia was significantly faster in posterior-exposed animals compared to those of the anterior-exposed and sham-irradiated animals. Furthermore, the posterior-exposed rats took a significantly shorter time to regain their righting reflex than both the anterior-exposed and sham-irradiated animals.