Neuroimmunology: modulation of the hamster immune system by photoperiod

Groups of adult male Syrian hamsters were kept in a long photoperiod (LD 14:10) or a short photoperiod (LD 10:14). After 12 weeks, half of the animals in each light:dark cycle were immunized with an immunogenic amino acid polymer. Exposure to short photoperiod was associated with a significant reduction in testicular, accessory sex organ, splenic and brown fat weights. However, photoperiod length did not influence whole body, thymic, adrenal or kidney weights. Spleens of immunized animals in the long photoperiod were significantly heavier than those of unimmunized animals in the long photoperiod, and both were heavier than spleens from immunized or unimmuized animals in the short photoperiod. This reflected increased splenic lymphocyte and macrophage counts. However, there was no difference in antibody production between animals kept in different photoperiods. These results demonstrate that the daily photoperiod length affects both hamster reproductive competence as well as selected immune parameters (splenic weight and mononuclear cell hyperplasia) but does not alter antibody production.     

Morphological observations of the fetal rat spleen during prolonged gestation

The ultrastructure of splenic cells and frequency of cell types were examined in fetal rats during progesterone-induced (P23, 24, 25) and surgically-induced (S23, 24, 25) prolonged gestation, and compared to term (T) fetuses and newborn animals (N1, N2, N3). Statistical analysis revealed an increase in numbers of erythroblasts and a decrease in numbers of neutrophils in post-term fetuses distinct from that seen in term and newborn animals. However, there were also significant differences between the post-term groups: the frequency of erythrocytes and total number of cells were higher in the drug-treated group, despite similar splenic weights in the two. The results are interpreted as a response by the spleen (increased erythropoiesis) to fetal hypoxia, which is known to exist during prolonged gestation.     

Lymphocyte plasma membranes. III. Composition of lymphocyte plasma membranes from normal and immunized rats

Isolated plasma membranes of thymic and splenic lymphocytes from unimmunized and immunized rats of the inbred ACI and F344 strains were analyzed for chemical and enzymatic composition, for membrane protein patterns by polyacrylamide gel electrophoresis and for membrane-associated immunoglobulins. After immunization, the thymic and splenic lymphocyte membranes from F344 rat contained less carbohydrate and higher phospholipid contents than control animals. In both ACI and F344 inbred rat strains the membrane phospholipid to cholesterol weight ratio increased significantly after immunization. The electrophoretic patterns of solubilized membrane proteins and of iodinated external membrane proteins were similar in unimmunized and immunized animals.When thymic and splenic lymphocytes of normal or immunized animals were surface radioiodinated, solubilized in Triton X-100, NP-40 or 10 M urea in 1.5 M acetic acid and analyzed by immunoprecipitation, labeled IgM immunoglobulin was recovered from thymic lymphocytes but both labeled IgG and IgM were recovered from splenic lymphocytes. However, when unlabeled isolated plasma membranes were solubilized in 1% Triton X-100 and analyzed by immunodiffusion in agarose gels, both IgG and IgM were identified in thymic and splenic cells.     

Underfeeding and exposure to short photoperiod alters rat pineal and Harderian gland lysosomal enzyme activities

Harderian gland (HG) weight and lysosomal enzyme activity were evaluated after 21-day-old female rats were singly caged in a long (LP; 14:10 LD) or short (SP; 8:16 LD) photoperiod and fed on one of two dietary regimens (fed ad libitum or 50% underfed) for 50 days; an additional fed and an underfed group of animals in LP were injected every afternoon with 100 micrograms melatonin. Absolute HG weights were significantly lower in all underfed groups compared to their respective fed controls or to the LP fed control group. Absolute HG weights of underfed rats in SP were significantly lower than the underfed rats in LP. Relative HG weights (mg/100 g body wt) were significantly higher in the underfed saline or melatonin-treated groups compared to their respective fed controls; however, HG of the underfed SP group were not different from SP-fed controls. No significant differences in HG acid phosphatase, hexosaminidase, and beta-glucuronidase activities were observed in any of the treatment groups maintained in LP. Acid phosphatase, hexosaminidase, and beta-glucuronidase activities were significantly elevated in HG of underfed animals maintained in SP compared to their respective fed controls or to the LP-underfed group. Both the underfed control and the underfed-melatonin treated groups had lower pineal protein values than their respective fed groups; underfed animals in 8:16 LD had similar pineal protein values compared to those of the fed control group in SP. Significant effects of photoperiod and underfeeding with no interaction between these variables were observed on pineal acid phosphatase. The fed group maintained in 8:16 LD had significantly higher acid phosphatase activity than the fed group kept in 14:10 LD. In conclusion, underfeeding resulted in severely reduced body weights and absolute Harderian gland weights. Increased activity in certain lysosomal enzymes occurred in both the pineal and Harderian gland and in some instances this was dependent upon the light cycle and dietary regimen to which the animals were exposed.     

Lymphoid tissue responses to perfluorocarbon emulsion in rats: time course effects relative to immune challenge

1. The effects of either intraperitoneal (i.p.) or intravenous (i.v.) injection of low doses (10 ml/kg) of the commercial emulsion, Fluosol-DA 20% (F-DA), on lymphoid tissues and antibody production against sheep red blood cells (SRBC) have been studied relative to the timing of immunization in rats. 2. Spleen and liver weights were significantly increased in response to injection of F-DA although no consistent pattern was observed. 3. Thymus weight was decreased following F-DA injection in some experimental groups whereas mesenteric lymph node (MLN) weights were unchanged throughout. 4. The mean plasma antibody titre to SRBC was significantly increased in some groups of animals injected with F-DA both before or after immunization; maximum titres were observed following injection of emulsion simultaneously with SRBC. 5. These results show that lymphoid tissue weights and plasma antibody titres in rats immunized with SRBC vary according to the timing and route of a previous or subsequent injection of F-DA.     

Reproductive Performance of Sows Supplemented with Dietary L-carnitine over Three Reproductive Cycles

The effect of L-carnitine supplementation during pregnancy and lactation on the reproductive performance of sows was studied in two separate trials over three reproductive cycles. Both trials were identical in design and conduct but were performed with different animals. The trials comprised of a total of 127 sows (trial 1) and 100 sows (trial 2) which were divided into control and treatment groups. All animals were fed individually and received basic feed mixtures with low native carnitine concentrations. The rations of the sows in the treated group were supplemented with 125mg L-carnitine per head and day during pregnancy and 250mg L-carnitine per head and day during lactation. The animals of the control group received identical feed mixtures in identical amounts, but without the L-carnitine supplement. In the first trial, 212 litters were produced and evaluated for number and body weight of the animals, in the second trial, 173 litters were produced. L-carnitine supplementation significantly increased body weight gains of the sows between day 1 and day 85 of weaning. The number of born piglets, stillborn piglets and piglets fit for rearing was not influenced by dietary L-carnitine supplementation. However, L-carnitine supplementation significantly increased the weights of piglets and litters at birth, weight gains of litters during suckling and weights of litters at weaning. These effects of L-carnitine were seen in both trials; they were independent of the age of the sows and remained over three reproductive cycles in which the sows where continuously treated with L-carnitine. Overall, the study shows that dietary supplementation with L-carnitine during pregnancy and lactation improves the reproductive performance of sows over several reproductive cycles, independent of the age of the sows.     

Correlation of histological an histometric changes in rats testes treated with chloroquine phosphate.

Histological and histometric changes in the testes of albino Wistar rats were correlated. Wistar rats weighing between 180-240g were randomly divided into three groups of ten rats each. One group served as control and the rats were given normal saline. The second and third groups received 2mg/kg and 4mg/kg body weights of chloroquine phosphate daily for thirty days respectively. Seminiferous tubules of animals treated with chloroquine phosphate were irregular in shape and were also isolated compared to control. Marked disruption of the inter-tubular stroma of testes in the treated groups was also observed. Histometric variations in testicular tissue was observed in the experimental animals following treatment with chloroquine phosphate. The 2mg/kg body weight and 4mg/kg body weight animals recorded significantly lower [P< 0.05] relative germinal epithelial volume of 43.95 % and 32.70 % respectively when compared to the control (51.75 %). The volume of stroma in the third group (49.33 %) was significantly higher [P < 0.05] when compared to the control (16.83 %) and 2mg/kg body weight rats (22.83 %). We observed negative correlation coefficient between lumen and seminiferous tubular volume in the control group compared to the other groups which showed a positive correlation. Correlation between germinal epithelium and seminiferous tubular volume were positive in all groups. These findings have thrown more light on recognized histological changes by accurately grading these changes which offers objectivity and increased precision compared with direct visual appraisal.     

Experimental cardiac necrosis in hypobaric and anemic hypoxia.

Resistance to isoproterenol-induced cardiac necrosis (IPRO) was compared in rats exposed to two types of hypoxia (i.e., hypobaric and anemic). IPRO was induced by two consecutive, subcutaneous injections of isoproterenol (80 mg/kg) at 24-h intervals. The animals were killed on the third day and the severity of the lesion was evaluated on a 0 (no damage) to 4 (severely damaged) scale. White male rats (HA) were exposed in a barometric chamber to a simulated altitude of 7,000 m (307 mmHg) for 4 h/day for 24 days. Two groups of control rats were kept at sea level; one group (SLA) was the same age and one group (SLW) was the same weight as the altitude-exposed rats. The HA rats were significantly more resistant to IPRO with a mean necrogenic rating of 1.8 compared to 3.3 for the SLA and SLW rats. Infant rats (AA) were made anemic by feeding full-cream milk and glucose for 100 days after weaning. Two groups of control animals were fed a standard laboratory diet; one group (AC) was the same age and one group (AW) was the same weight as the AA rats. There was no significant difference in the necrogenic ratings of the AA (3.3), AC (3.5), or WC (3.7) hearts. Thus, hypobaric hypoxia affords some protection against IPRO which is not afforded by anemic hypoxia. Similarities and differences in the two hypoxias are discussed.     

Adrenalectomy and Castration in the Genetically Obese (OB/OB) Mouse

The present studies have tested the hypothesis that adrenalectomy could modify the phenotypic expression of genetic obesity by examining the effects of adrenalectomy on the function of the gonadal system in lean and ob/ob mice. Corticosterone concentrations were undetectable in the adrenalectomized animals. Adrenalectomy significantly slowed the weight gain of obese mice in comparison to sham-adrenalectomized controls. Gonadectomy had no independent effect on weight gain. The testes, prostate, and seminal vesicles in the ob/ob mice were significantly smaller than in the lean animals. Castration lowered the weights of the prostate and seminal vesicles in the lean mice to weights close to those observed in the castrated ob/ob mice. Castration significantly increased the concentrations of LH and FSH in both ob/ob and lean mice, but the absolute concentrations were higher in the lean mice in both conditions. Adrenalectomy per se had no effect on the concentration of LH, FSH, or testosterone or on the weights of the prostate or seminal vesicles. These data indicate that adrenalectomy has no effect on the physiologic control of the reproductive system in genetically obese mice, and are consistent with the hypothesis that the defect in the ob/ob mouse is a modulator of steroid action which over expresses glucocorticoid effects and under expresses gonadal steroid effects.     

Studies on the (pro) insulin biosynthesis of islets of Langerhans of sand rats (Psammomys obesus).

By feeding a regular laboratory chow, sand rats (Psammomys obesus) from our breeding colony gained different body weights, though they received approximately the same quantity of calories. Sand rats, reaching a body weight above 160 g (group B) showed significantly increased blood glucose values in contrast to the animals with a body weight under 160 g (group A). Isolated pancreatic islets of these two groups of sand rats were incubated with [3H]-leucine to study the incorporation of this amino acid into proinsulin and insulin. The incorporation into proteins of pancreatic islets of sand rats of group B was stimulated by 0.45 mg and 3.0 mg/ml glucose. In group A there was no further stimulation from 0.45 mg to 3.0 mg/ml glucose. Insulin secretion could be stimulated by glucose in both groups, but the stimulation was stronger in group B than in group A.     

Anti-obesity potential of almond (Prunus dulcis) in experimental animals under cafeteria and atherogenic diets

Background & objectivesNatural dietary supplements are progressively getting famous to supplant synthetic substances particularly in chronic morbidities. The aim of this study was to evaluate the anti-obesity potential of almond on the normal, Cafeteria, and Atherogenic diets.Materials and methodsParameters such as change in body weight, body temperature, lipid profile, organ weights, and fat pad weights were assessed. Central Nervous System related studies (Despair Swim test and Elevated Plus maze test) were also performed to comprehend the effect of the diets, and almond on the brain. All of the experimental animals were randomly assigned to one of three diet categoriesregular, cafeteria, or atherogenic, and fed those diets for 40 days. Each diet had the control group, standard drug group and three almond groups (low dose: 50; medium dose: 100 and high dose: 200 mg/kg body weight). Body weight was recorded every alternate day. On 40th day, body temperature was measured. On day 41, lipid parameters, organ weights, fat pad weights and the CNS parameters were evaluated. ANOVA followed by Duncans Multiple Range Test were used for statistical analysis.ResultsTreatment of animals with either a low or high dose of almond as well as a standard herb prevented a rise in body weight significantly (p = 0.01) in all three diet groups. When a regular diet was replaced with a cafeteria and atherogenic diet, the serum levels of triglycerides and LDL increased significantly, while HDL levels decreased significantly. Overall, almond preparation reduced lipid parameters, organ weights, fat-pad weights, and stabilized CNS parameters substantially.Interpretation & conclusionThe almond high dose was the most effective of all the almond preparations. Our study suggests that chronic administration of almond independently reduces the body weight in experimental animals.     

Age-dependent effects of chronic hypoxia on renin-angiotensin and urinary excretions

The mechanisms regulating water, electrolyte, and blood volume homeostasis continue to mature in early postnatal life, and this maturation may be altered by perturbations of volume or cardiovascular status. To evaluate the long-term effects of chronic hypoxia on water balance, urinary electrolyte excretion, heart weights, systemic arterial pressure, and components of the renin-angiotensin system, male Sprague-Dawley rats were exposed to periods of simulated altitude of 10,000 ft up to 90 days of age beginning at 2 or 30 days of age. Altitude exposure of both neonatal and adult rats was associated with increases in urine output and water intake after 30 days of exposure, and right ventricular (RV) hypertrophy at all ages was examined. However, the percent increase in urine output, water intake, and RV hypertrophy was numerically greater in neonates. Neonates also had increases in urinary sodium and potassium excretion after 30 days of exposure. Plasma renin activity and serum angiotensin-converting enzyme (ACE) activity were not affected, but plasma renin substrate was reduced in both neonatal and adult altitude-exposed rats. Lung ACE activity was also decreased in altitude-exposed neonates. These data indicate that the degree and, in some cases, the nature of these homeostatic responses varies with age during long-term hypoxia.     

Schistosomatium douthitti: biochemical and morphological effects of an experimental infection in mice

The pathophysiological changes that occur in mice experimentally infected with Schistosomatium douthitti were studied. Male ICR mice, 6-8 weeks in age, were exposed to 100 cercariae of S. douthitti from infected snails (Lymnaea catascopium) and sacrificed weekly for a total of 13 weeks. Liver homogenates, serum samples, and histological sections of liver tissue were examined. Results showed that body weights of animals with prepatent infections were higher than those of corresponding controls. After patency, which occurred at 5 weeks, body weights were lower and liver weights were higher resulting in significantly increased liver weight/body weight ratios. Hematocrit values declined progressively in patent infections. Total cholesterol in liver was generally higher in the parasitized groups reaching significance during patency. Values rose with age in both control and parasitized groups, but sooner in the latter. Free cholesterol was increased in the liver of animals with patent infections. Total lipid content of the liver was reduced in the infected animals throughout the study. Both liver glycogen and serum glucose levels in the infected animals rose over the control values. The activity of alkaline phosphatase (E.C.3.1.3.1) was elevated in liver tissue of infected mice. Glutamic-pyruvic transaminase (E.C.2.6.1.2) activity was higher in serum but lower in the livers of animals harboring patent infections. Total bile salt concentration in parasitized animals did not differ appreciably from control values; however, gallbladders were enlarged five times in the infected animals. Histologically, liver sections from infected mice showed granulomas in various stages of formation and degeneration. Granulomas contained from 1 to 40 schistosome eggs. After 6 weeks of infection, granulomas were characterized by many neutrophils and monocytes. Few lymphocytes and eosinophils were present. As the granulomas developed, fibroblasts and connective tissue became more prominent. Glycogen deposits were observed surrounding granulomas and were increased in older infections. Adult worms contained abundant amounts of glycogen and cholesterol in their parenchymal tissues.     

Effects of increased energy expenditure on weight gain and adiposity in the LA-corpulent rat

Groups of lean or pre-obese LA/N-cp rats were subjected to a program of vigorous exercise (less than 4 hr/day) or remained sedentary from 6 weeks until 12 weeks of age. Sedentary pre-obese rats gained weight twice as rapidly as sedentary lean rats. Exercise treatment resulted in greater decrements in body wt in obese than in lean rats, but did not result in absolute weight loss in either group. At 12 weeks of age, fat pad weights in principle depots were 10-15 times greater in corpulent than in lean rats and were significantly smaller in the exercised groups of both phenotypes, and corresponded with lower relative adiposity compared to corresponding sedentary groups. Heart weights were greater in corpulent than lean, while gastrocnemius muscle weights were similar in both phenotypes. Exercise was without effect on the weight of either muscle tissue in either phenotype. Interscapular brown adipose tissue weights and the IBAT:BW ratio were greater in obese than in lean rats. IBAT weights were lower in exercised than sedentary rats of either phenotype, but the IBAT:BW ratio was lower only in the obese exercised rats. In sedentary rats, L-alpha-glycerophosphate dehydrogenase and malic enzyme activity were greater in obese than lean, and exercise treatment resulted in increased L-alpha-glycerophosphate dehydrogenase and malic enzyme only in lean rats. These results are consistent with a redistribution of energy expenditure from energy storing to energy dissipating pathways following vigorous exercise, resulting in slowed rates of weight gain and body fat accretion in both lean and obese animals, with the most significant decrements among pre-obese rats.     

Splenic hypertrophy and extramedullary hematopoiesis induced in male Syrian hamsters by short photoperiod or melatonin injections and reversed by melatonin pellets or pinealectomy

Adult male Syrian hamsters either placed in a short photoperiod alone or kept in a long photoperiod and given daily afternoon injections of the pineal indole melatonin (25 micrograms) exhibited splenic hypertrophy and extramedullary hematopoiesis in addition to a marked regression in testicular weight. The testicular regression as well as the changes in spleen weight and histology could be prevented if the animals in short photoperiod were either pinealectomized or implanted subcutaneously with a pellet containing 1 mg melatonin. Female Syrian hamsters given afternoon injections of melatonin for 7 or 12 weeks had ovaries devoid of corpora lutea; additionally, these animals had reduced relative spleen weights compared to the control animals. In conclusion, it is apparent that spleen weight varies with the functional status of the gonads. Splenic hypertrophy accompanied by pineal-induced testicular regression in males may be related to splenic extramedullary hematopoiesis.     

Ventricular weights in guinea pigs acclimated to cold plus hypoxia

Weanling male guinea pigs (Cavia porcellus), 2-3 weeks of age, with initial body weights of 207-271 g were exposed for 2-16 weeks to constant cold (6 degrees C) and hypoxia (PO2 = 85 Torr) equivalent to 4800 m above sea level. Their growth rates and body weights did not differ from those of control animals of the same age maintained under normoxic conditions (22 degrees C, PO2 = 133 Torr). After 2, 3, 4, 6, 10, or 16 weeks exposure the animals were sacrificed, the hearts were removed, the ventricles were separated and weighed, and myoglobin concentrations were determined. Total heart weight as well as both right and left ventricular weights increased linearly with age. By the second week of exposure of the guinea pigs to cold plus hypoxia the total heart and right ventricular weights were 25 and 50% greater than those of the normoxic control animals. Both weights increased at greater rates than those of the controls until Week 6 and then remained at 30 and 80% throughout the 16th week. The weights of the left ventricles in these animals were only slightly greater than those of the controls. In spite of the severe right ventricular hypertrophy these animals showed no clinical signs of right heart failure. Myoglobin concentrations were significantly greater in both ventricles for the cold-plus-hypoxic animals than for the controls.     

Ursolic acid ameliorates thymic atrophy and hyperglycemia in streptozotocin–nicotinamide-induced diabetic mice

The purpose of this study was to assess the effects of low-dose ursolic acid (UA) on glycemic regulation and immune responses in streptozotocin–nicotinamide (STZ/NA)-induced diabetic mice. Diabetic mice were supplemented with two different doses of UA (0.01 and 0.05%, w/w) or metformin (0.5%, w/w) for 4 weeks. Compared with the untreated diabetic group, UA and metformin significantly improved blood glucose, glycosylated hemoglobin, glucose tolerance, insulin tolerance and plasma leptin levels as well as aminotransferase activity. The plasma and pancreatic insulin concentrations were significantly higher in both UA groups than in the untreated diabetic group. Supplementation with metformin increased the pancreatic insulin level without a change in the plasma insulin level. The relative thymus weights were lower in the untreated diabetic group compared to the non-diabetic group; however, the UA or metformin group had significantly improved thymus weights. Mice receiving UA or metformin supplementation had increased CD4⁺CD8⁺ subpopulations in the thymus compared to the untreated diabetic mice. Concanavalin A-stimulated splenic T-lymphocyte proliferation and single-positive (CD4⁺ and CD8⁺) subpopulations were significantly higher in the UA-supplemented diabetic groups than in the untreated diabetic group, but lipopolysaccharide-stimulated B-lymphocyte proliferation and the CD19⁺ subpopulation were not significantly different among the groups. In the STZ/NA-induced diabetic mice, metformin increased the splenic T-lymphocyte CD4⁺ and CD8⁺ cell numbers without any change in T-lymphocyte proliferation. Both doses of UA lowered splenic IL-6 levels, whereas metformin increased IFN-γ, IL-6 and TNF-α levels compared to the untreated diabetic mice. These results suggest that low-dose UA may be used as a hypoglycemic agent and immune modulator in non-obese type 2 diabetic mice.     

Immunotoxicity of repeated low level exposure to T-2 toxin,a trichothecene mycotoxin,in CD-1 mice

Male CD-1 mice were gavaged with T-2 toxin (0.0–5.0 mg/kg body weight) every third day. Body weight gain was depressed by exposure to 2.5 mg/kg, or greater, T-2 toxin; this was not associated with decreased food intake. The weights of the liver, kidney, spleen, and thymus were affected by two weeks exposure to T-2 toxin. However, a persistent effect after four weeks was observed only for the thymus. Peripheral leucocyte counts were elevated in the highest dose groups after two and four weeks. Thymidine uptake by cells not simultaneously exposed to mitogen was increased in splenic cell cultures of mice exposed to 2.5 mg/kg T-2 toxin for two or four weeks. Phytohemagglutinin stimulation of splenic lymphocytes following two weeks of exposure was depressed in the 2.5 mg/kg dose group; this phenomenon was not observed after four weeks exposure. Response to pokeweed mitogen increased after four weeks of exposure to 2.5 mg/kg T-2 toxin. A delayed-type hypersensitivity response decreased following two weeks exposure to levels greater than 0.02 mg/kg. Production of I g M class antibodies by splenic lymphocytes, evaluated by a hemolytic plaque response to sheep erythrocytes, was depressed in the 2.5 mg/kg dose group after two weeks exposure to T-2 toxin. The sensitivity and specificity of T-2 toxin immunotoxicity was indicated by the various parameters evaluated.     

Effects of a novel perfluorochemical emulsion on lymphoid tissues and immunocompetence in rats: time course effects relative to immunological challenge

1. The effects of intravenous (i.v.) injection of low doses of a novel perfluorochemical (PFC) emulsion on lymphoid tissues and antibody production against i.v.-injected sheep red blood cells (SRBC) have been studied relative to the timing of immunization in rats. 2. Spleen and, to a lesser extent, liver weights were significantly increased in response to injection of emulsion but no consistent pattern was observed. 3. Thymus weight was consistently decreased following injection of emulsion; in contrast, mesenteric lymph node (MLN) weights were unchanged throughout except for a significant increase in animals injected with emulsion 24 hr prior to immunization. 4. The mean plasma antibody titre to SRBC showed a variable response in animals receiving the emulsion: titres were significantly increased in rats injected with emulsion 1 hr prior to immunization whereas they were significantly reduced in animals injected with emulsion 7 days before SRBC. 5. These results show that lymphoid tissue weights and plasma antibody titres to SRBC vary according to the time of a previous or subsequent injection of PFC emulsion.     

Brain Maturation Following Administration of Phenobarbital, Phenytoin, and Sodium Valproate to Developing Rats or to Their Dams: Effects on Synthesis of Brain Myelin and Other Subcellular Membrane Proteins

Abstract: The anticonvulsant drugs phenobarbital, phenytoin, sodium valproate, and phenytoin-sodium valproate in combination were administered daily to (a) pregnant rats starting on the 5th day after conception, and continued through 17 days postpartum, or (b) to developing rats between 3 and 17 days of age. Each drug was prepared in water and administered at either a therapeutic dose (TD), three times therapeutic dose (³TD), or 9TD. Drug administration had no discernible effect on litter size or sex ratio in the offspring; however, phenobarbital administration to dams caused small but significant reductions in birth weights. Body weights of developing rats treated with anticonvulsant drugs either via dams or directly by intraperitoneal injection lagged behind controls. At 20–24 days of age the brain weights of the offspring of phenobarbital (9TD)-exposed dams lagged control weights by 5% whereas brain weights in the offspring of the other treated groups were indistinguishable from controls. In contrast, administration of phenobarbital directly to developing rats caused no significant brain weight deficits whereas significant deficits were observed with phenytoin (9TD), sodium valproate (9TD), and phenytoin-sodium valproate (9TD) in combination. At 20–24 days of age the relative incorporation of radioactive leucine into purified myelin and crude nuclear proteins of drug-treated rats or the offspring of drug-treated dams was reduced by 10–20% in all cases. Dose-related differences were not observed however, and the effects of phenytoin and sodium valproate in combination approximated those of phenytoin administered alone.