A persistent deficit of serotonin neurons in the offspring of ethanol-fed dams: protective effects of maternal ipsapirone treatment

An earlier study from this laboratory found a significant reduction in the density of serotonin (5-HT) neurons in the dorsal and median raphe and in the B9 complex of postnatal day 5 (PN5) offspring of female rats that consumed ethanol on a chronic basis prior to parturition. In addition, we demonstrated that maternal treatment with the 5-HT(1A) agonist ipsapirone (3 mg/kg) prevented the ethanol-associated reduction in 5-HT neurons. The present investigation examined whether there was a persistent deficit of 5-HT-immunopositive neurons in the dorsal and median raphe of the offspring of ethanol-fed dams. We also evaluated whether a lower ipsapirone dose (1 mg/kg) was protective to developing 5-HT neurons in the offspring of ethanol-fed dams. The offspring of ethanol-fed dams exhibited an apparent lasting reduction in the density of 5-HT neurons in the dorsal and median raphe. The density of 5-HT neurons in control offspring was comparable at PN5 and PN19, but at both ages the offspring of ethanol-fed dams had a significant deficit of 5-HT neurons in the dorsal and median raphe. The lack of recovery in the density of 5-HT-immunopositive neurons in the offspring of ethanol-fed dams between PN5 and PN19 suggests and that the reduction was long lasting. The protective effects of ipsapirone appeared to be dose dependent. The density of 5-HT neurons in the dorsal and median raphe of PN5 (prior study) and PN19 offspring of ethanol-fed dams that were treated with 3 mg/kg of ipsapirone between gestational day 13 (G13) and G20 was comparable to that of control offspring. However, the effects of maternal treatment of ethanol-fed dams with the 1 mg/kg dose were variable, and some abnormalities were detected in the offspring of ipsapirone-treated control dams.     

Effect of perinatal polybrominated biphenyl exposure on acquisition and performance of an autoshaping paradigm

Pregnant Sprague-Dawley rats received oral doses of 0, 0.2 or 2 mg/kg/day polybrominated biphenyls (PBB) as fireMaster BP-6 (BP-6) from day 6 of gestation through day 24 postpartum. At approximately 6 months of age male and female offspring were food-deprived to 80% of their free-feeding weights and subjected to four phases of an autoshaping paradigm. Acquisition of Phase I, a VI-90 second schedule of responding, was significantly delayed for female offspring from dams administered 2 mg/kg/day BP-6; a trend toward delayed acquisition was observed in all other PBB-exposed animals. No BP-6-related difference in latency to respond during this phase was observed. Male offspring from dams administered BP-6 appeared to acquire Phase II responding (a FI-90 second contingency) at a faster rate than did control males. In contrast, BP-6-exposed females acquired Phase II responding at a somewhat slower rate than did control females. The sex-related difference in responding may involve a rate-dependent influence, as control females acquired Phase II responding much more quickly than did control males. Control males and females acquired Phase III (FR-20 responding) at approximately the same rate. No BP-6-related deficits were observed during the initial few days of acquisition of FR-20 responding. However, BP-6-exposed male offspring tended to respond more than did control males after this time. BP-6-exposed females tended to respond less than did control females only as the responding of controls approached an asymptote. Phase IV involved FR-20 responding following challenge with d-amphetamine or chloral hydrate; no significant BP-6-related changes in disruption of this behavior were observed.     

Prenatal exposure to ethinylestradiol elicits behavioral abnormalities in the rat

Pregnant rats were i.p. injected with a solution of 17alpha-ethinylestradiol (15 microg kg(-1)) every day between day 9 and day 14 of pregnancy and the behavior of the offspring was compared to that of rats born from dams injected with the vehicle only during the same gestational period. The percentage of neonatal death was dramatically high in the prenatally treated group. Growth of the surviving animals was even better than that of controls, but when adult, they exhibited a number of behavioral abnormalities: increased spontaneous motor activity, decreased exploratory behavior, impaired cognitive processing, qualitatively different exploratory drive, and/or persevering behavior, increased anxiety-like behavior and social neophobia. These behavioral alterations, which resemble a number of psychiatric syndromes, suggest that ethinylestradiol altered the ontogenesis of different parts of the central nervous system involved in cognitive and emotional processes. However, it cannot be excluded that the changes in behavior of ethinylestradiol exposed offspring were due to the abnormal maternal behavior of the estradiol treated dams.     

Prenatal exposure to glucocorticoids affects body weight,serum leptin levels,and hypothalamic neuropeptide-Y expression in pre-pubertal female rat offspring

Glucocorticoid secretion is a key endocrine response to stress. It has been reported that prenatal stress induces long-lasting alterations in body weight regulation systems, which persist after the stress has ceased. In this study, the long-term effects of prenatal glucocorticoid exposure on body weight changes and the expression of appetite-regulating factors were examined in female rats. Pregnant rats were given normal drinking water (control) or dexamethasone (1 μg/mL) dissolved in drinking water (DEX) from day 13 of pregnancy until delivery. Then, the body weight change, serum leptin levels, and hypothalamic NPY mRNA levels of their offspring were examined. The DEX dams gained significantly less body weight during pregnancy than the control dams. The DEX dams’ offspring exhibited a significantly lower birth weight than the offspring of the control dams, and the same was true for body weight at postnatal days 20 and 28. The offspring of the DEX dams displayed significantly higher serum leptin levels and significantly lower hypothalamic NPY mRNA levels compared with the offspring of the control dams. Significant inverse correlations were detected between body weight and the serum leptin level, and between the serum leptin level and the hypothalamic NPY mRNA level. On the other hand, a significant positive correlation was detected between body weight and the hypothalamic NPY mRNA level. These results indicate that leptin production is increased in a long-lasting manner in offspring exposed to glucocorticoids during the prenatal period and that this results in attenuated body weight gain and hypothalamic NPY expression during the pre-pubertal period.     

Prenatal and early postnatal exposure to zimelidine: behavioral, neurochemical and histological findings in rats

Zimelidine (5 mg/kg/day s.c.) was administered to pregnant rats from day 10 to day 20 of gestation. The development and later open field and learning capacities of their offspring were compared to those of saline injected and untreated dams. The development and behavior of prenatally zimelidine exposed offspring resembled those of the untreated rather than the saline injected group. Pups that were nursed by zimelidine treated mothers, however, showed behavioral deficits compared to those that were nursed by saline injected dams. Prenatal or early postnatal exposure to the 5HT uptake inhibitor zimelidine did not affect 5HT uptake and release measured at 3 months of age. Histological examination of major organs of prenatally zimelidine exposed animals showed no pathological changes.     

Brain myelination in the offspring of ethanol-treated rats: in Utero versus lactational exposure by crossfostering offspring of control, pairfed and ethanol treated dams

Pregnant Long-Evans rats were received on day 5 of gestation and divided into 4 treatment groups: (1) 27% calories provided as ethanol in a liquid diet; (2) pairfed i.e., isocaloric liquid diet restricted to match group (1); (3) liquid diet provided ad libitum; and (4) laboratory chow and water provided ad libitum. Litters were culled to 8 pups at birth and crossfostered across dams in all 4 groups to provide offspring falling into 16 different experimental groups, including some exposed to ethanol in utero only and some exposed only during lactation. At birth, blood alcohol levels of dams, culled pups and alcohol levels in the stomach contents of culled pups were measured. All pups were weaned and fed laboratory chow and water ad libitum from 21 days onward. At ages 16, 21, 30 and 52 days, pups were sacrificed, and organ/body weight ratios and brain myelin concentrations were determined. Ethanol treated dams had longer gestational periods. The offspring of ethanol treated dams which were crossfostered to pairfed and well nourished dams during lactation had delayed eye opening, persistent lag in body growth and slightly lower brain myelin concentrations. Offspring of dams which were either pairfed or well nourished during gestation, but crossfostered during lactation to ethanol treated dams, had abnormal organ weights, abnormal brain weights and severely depressed brain myelin concentrations persisting through 52 days of age. Thus, lactational ethanol effects on brain myelin were more severe than gestational effects; body growth was affected more severely by gestational exposure, and gestational effects were generally less severe with adequate nutrition.     

Prenatal exposure to a pro-inflammatory stimulus causes delays in the development of the innate immune response to LPS in the offspring

Growing evidence suggests that maternal health during the prenatal period is a critical determinant of adult immuno-competence. This study aimed to characterise the innate immune response to bacterial exposure in rat offspring following maternal exposure to a pro-inflammatory stimulus. The offspring's innate immune responses were investigated at four developmental timepoints in the rat by determination of immune cell subtypes and TNF-alpha and IL-1beta response to in-vivo LPS exposure. The pre-weaned offspring of exposed dams demonstrated no immune response to the LPS challenge, whereas control offspring responded with a typical elevation in cytokine levels. In pubescence no differences were observed between the responses of the control and exposed offspring. In adulthood and senescence, offspring of endotoxin treated dams had significantly less monocytes in circulation than control offspring and differential sex effects were only evident in these older animals. The developmental profile of immune functioning following prenatal immune activation has not previously been demonstrated. This study highlights the prenatal period as one of importance in determining later immune function.     

Additive effects of maternal iron deficiency and prenatal immune activation on adult behaviors in rat offspring

Both iron deficiency (ID) and infection are common during pregnancy and studies have described altered brain development in offspring as a result of these individual maternal exposures. Given their high global incidence, these two insults may occur simultaneously during pregnancy. We recently described a rat model which pairs dietary ID during pregnancy and prenatal immune activation. Pregnant rats were placed on iron sufficient (IS) or ID diets from embryonic day 2 (E2) until postnatal day 7, and administered the bacterial endotoxin, lipopolysaccharide (LPS) or saline on E15/16. In this model, LPS administration on E15 caused greater induction of the pro-inflammatory cytokines, interleukin-6 and tumor necrosis factor-α, in ID dams compared to IS dams. This suggested that the combination of prenatal immune activation on a background of maternal ID might have more adverse neurodevelopmental consequences for the offspring than exposure to either insult alone. In this study we used this model to determine whether combined exposure to maternal ID and prenatal immune activation interact to affect juvenile and adult behaviors in the offspring. We assessed behaviors relevant to deficits in humans or animals that have been associated with exposure to either maternal ID or prenatal immune activation alone. Adult offspring from ID dams displayed significant deficits in pre-pulse inhibition of acoustic startle and in passive avoidance learning, together with increases in cytochrome oxidase immunohistochemistry, a marker of metabolic activity, in the ventral hippocampus immediately after passive avoidance testing. Offspring from LPS treated dams showed a significant increase in social behavior with unfamiliar rats, and subtle locomotor changes during exploration in an open field and in response to amphetamine. Surprisingly, there was no interaction between effects of the two insults on the behaviors assessed, and few observed alterations in juvenile behavior. Our findings show that long-term effects of maternal ID and prenatal LPS were additive, such that offspring exposed to both insults displayed more adult behavioral abnormalities than offspring exposed to one alone.     

Neurobehavioral maturation of offspring from epileptic dams: Study in the rat lithium–pilocarpine model

In the present study, we explored the consequences of epilepsy on the neurobehavioral development of the offspring in a rat model of spontaneous epilepsy, the lithium–pilocarpine model of temporal lobe epilepsy not dependent on genetic factors and in animals not receiving any antiepileptic treatment. Status epilepticus was induced by lithium–pilocarpine in female rats. After the occurrence of spontaneous seizures the rats were mated and the neurobehavioral development of the offspring was explored. Rat pups were cross-fostered early after birth. We hence obtained pups born from or raised by epileptic or non-epileptic dams. On the dams, we performed a follow-up of maternal care during pregnancy. On the pups, we performed a follow-up of classical parameters of development such as body weight and eyelid opening, and subjected the pups to various tests representative of neurobehavioral maturation extending from postnatal day 4 (PD4) to PD30 (righting reflex, suspension time, negative geotaxis, open field, locomotor coordination and eight arm maze). Altogether our data show that rat pups born from or raised by epileptic dams develop as well as control pups raised by control dams. Intriguingly, pups born from lithium–pilocarpine exposed dams and raised by control mothers tend to have better scores than the two other groups in all tests. This indicates that the exposure to seizures during pregnancy is not harmful for the development of the fetus.     

Second generation effects of maternal alcohol consumption during pregnancy in rats

1. Previous studies have shown that when female rats are administered alcohol during pregnancy there are adverse effects on their progeny, including decreased birth weight and delayed neuromotor development. Evidence from several sources suggests alcohol exposure may contribute to cytogenetic abnormalities, suggesting the possibility of cross generational effects from prenatal exposure. 2. On day 1 of gestation female rats were randomly allocated to the Alcohol group, which received a liquid diet containing 5% (v/v) ethanol solution until parturition, the Sucrose control group, which received an identical diet, except that sucrose had been isocalorically substituted for ethanol, or the Chow control, which received standard laboratory chow. 3. When the offspring of these rats reached adulthood they were mated with drug-free rats and the development of their offspring was monitored. 4. In comparison with female pups whose sires had been exposed to alcohol in utero, the weight of pups descended from fetally-exposed dams increased more slowly from day 1 to day 7. 5. At five days of age, significant differences favouring the two control groups were found in latency to right for pups descended from fetally-exposed dams. 6. These data suggest that the effects of prenatal exposure to alcohol are more pervasive than previously thought and affect female pups to a greater extent than males.     

Individual differences in maternal response to immune challenge predict offspring behavior: contribution of environmental factors

Maternal infection during pregnancy elevates risk for schizophrenia and related disorders in offspring. Converging evidence suggests the maternal inflammatory response mediates the interaction between maternal infection, altered brain development, and behavioral outcome. The extent to which individual differences in the maternal response to immune challenge influence the development of these abnormalities is unknown. The present study investigated the impact of individual differences in maternal response to the viral mimic polyinosinic:polycytidylic acid (poly I:C) on offspring behavior. We observed significant variability in body weight alterations of pregnant rats induced by administration of poly I:C on gestational day 14. Furthermore, the presence or absence of maternal weight loss predicted MK-801 and amphetamine stimulated locomotor abnormalities in offspring. MK-801 stimulated locomotion was altered in offspring of all poly I:C treated dams; however, the presence or absence of maternal weight loss resulted in decreased and modestly increased locomotion, respectively. Adult offspring of poly I:C treated dams that lost weight exhibited significantly decreased amphetamine stimulated locomotion, while offspring of poly I:C treated dams without weight loss performed similarly to vehicle controls. Social isolation and increased maternal age predicted weight loss in response to poly I:C but not vehicle injection. In combination, these data identify environmental factors associated with the maternal response to immune challenge and functional outcome of offspring exposed to maternal immune activation.     

Interacting effects of oxazepam in late pregnancy and fostering procedure on mouse maternal behavior

The present study was designed to assess the proactive effects of late pregnancy benzodiazepine (BDZ) treatment on maternal behavior in the postpartum period, using cross-fostering procedures to control for the role of changes produced prenatally in the offspring. Outbred CD-1 mouse dams were treated with either oxazepam (OX, 15 mg/kg PO twice/day on pregnancy days 12-16) or vehicle (VEH). After parturition, entire litters were exchanged either within treatments (in-fostered groups, IF) or between treatments (cross-fostered groups, CF), while additional litters were left undisturbed (un-fostered groups, UF). The behavior of lactating dams was observed in their home cages at 4, 8, and 12 days postpartum. Maternal responses, particularly nursing, were reduced in the OX-UF and OX-CF conditions and either normal or enhanced in the OX-IF condition. Correspondingly, locomotor/exploratory activity was markedly enhanced in the former conditions and close to the control level in the latter condition. In sum, the fostering variable appeared to determine whether pups raised by dams treated previously with BDZ receive either insufficient or exaggerated maternal care. This points to the need for a better understanding of mother/pup interactions in studies aimed at characterizing drug and toxicant effects on offspring development.     

Maternal exercise during pregnancy ameliorates the postnatal neuronal impairments induced by prenatal restraint stress in mice

Clinical and preclinical studies have demonstrated that prenatal stress (PS) induces neuronal and behavioral disturbances in the offspring. In the present study, we determined whether maternal voluntary wheel running (VWR) during pregnancy could reverse the putative deleterious effects of PS on the neurodevelopment and behavior of the offspring. Pregnant CF-1 mice were randomly assigned to control, restraint stressed or restraint stressed + VWR groups. Dams of the stressed group were subjected to restraint stress between gestational days 14 and delivery, while control pregnant dams remained undisturbed in their home cages. Dams of the restraint stressed + VWR group were subjected to exercise between gestational days 1 and 17. On postnatal day 23 (P23), male pups were assigned to one of the following experimental groups: mice born from control dams, stressed dams or stressed + VWR dams. Locomotor behavior and pyramidal neuronal morphology were evaluated at P23. Animals were then sacrificed, and Golgi-impregnated pyramidal neurons of the parietal cortex were morphometrically analyzed. Here, we present two major findings: first, PS produced significantly diminished dendritic growth of parietal neurons without altered locomotor behavior of the offspring; and second, maternal VWR significantly offset morphological impairments.     

Device for monitoring locomotor activity of 120 animals: motility of offspring of dams exposed to haloperidol

A device using four infra-red light photocells per cage which monitor simultaneously the motility of 120 individual rodents, was developed at our institute. The measuring interval can be chosen freely, the starting time may be set freely and the test may last several weeks. The motility of the offspring (day 35-39) of dams exposed to the neuroleptic haloperidol during lactation was investigated, because of the important stage of the brain development in the neonatal age and of the relatively high concentration of haloperidol in the milk. Mice dams were treated sc. with a single dose (1.5 mg/kg) of haloperidol postnatally on day 3 to 6. Compared to the controls the body weight gain of treated (via milk) pups was reduced (controls = 72%, haloperidol = 30%) and the mortality was higher (controls = 10%, haloperidol = 77%) during the treatment period. The quantitative and qualitative analysis of the locomotor activity from day 35 to day 39 shows a distinct shift in the kind of motility: the locomotor activity of haloperidol offspring is significantly reduced while the number of activity phases is increased. It appears that there is a persistent alteration in the central nervous system that leads to a higher frequency but a lower efficacy of activity.     

Gestational stress induces post-partum depression-like behaviour and alters maternal care in rats

Gestational stress (GS) produces profound behavioural impairments in the offspring and may permanently programme hypothalamic-pituitary-adrenal (HPA) axis function. We investigated whether or not GS produced changes in the maternal behaviour of rat dams, and measured depression-like behaviour in the dam, which might contribute to effects in the progeny. We used the Porsolt test, which measures immobility in a forced-swim task, and models depression in rodents, while monitoring maternal care (arched-back nursing, licking/grooming, nesting/grouping pups). Pregnant rats underwent daily restraint stress (1 h/day, days 10-20 of gestation), or were left undisturbed (control). On post-parturition days 3 and 4, dams were placed into a swim tank, and time spent immobile was measured. GS significantly elevated immobility scores by approximately 25% above control values on the second test day. Maternal behaviours, in particular arched-back nursing and nesting/grouping pups, were reduced in GS dams over post-natal days 1-10. Adult offspring showed increased immobility in the Porsolt test, and also hypersecreted ACTH and CORT in response to an acute stress challenge. These data show that GS can alter maternal behaviour in mothers, and this might contribute to alterations in the offspring. GS may be an important factor in maternal post-natal depression, which may in turn detrimentally effect the offspring because depressed mothers do not sufficiently care for their offspring.     

Brief postpartum separation from offspring promotes resilience to lipopolysaccharide challenge-induced anxiety and depressive-like behaviors and inhibits neuroinflammation in C57BL/6J dams

Emerging evidence indicates an important role for neuroinflammation in depression. Brief maternal separation promotes resilience to depression in offspring, but relatively little is known about the effects of different durations of postpartum separation (PS) from offspring on anxiety and depressive-like behaviors in dams following immune challenge. Lactating C57BL/6J mice were subjected to no separation (NPS), brief PS (15 min/day, PS15) or prolonged PS (180 min/day, PS180) from postpartum day (PPD) 1 to PPD21 and then injected with lipopolysaccharide (LPS). Behavioral tests, including the open field test (OFT) and forced swimming test (FST), were carried out at 24 h after the injection. LPS resulted in anxiety and depressive-like behaviors in NPS dams and activated ionized calcium-binding adaptor molecule (Iba1), an important biomarker of microglia, in the hippocampus. However, compared with NPS + LPS dams, PS15 + LPS dams spent significantly more time in the center of the OFT (anxiety-like behavior) and exhibited lower immobility time in the FST (depressive-like behavior), which indicated a phenomenon of resilience. Furthermore, the activation of neuroinflammation was inhibited in PS15 dams. Specifically, levels of the Iba1 mRNA and protein were decreased, while the mRNA expression of NLR family pyrin domain containing 3 (NLRP3) inflammasome/interleukin-18 (IL-18)/nuclear factor kappa-B (NF-κB) was decreased in the hippocampus. Furthermore, positive linear correlations were observed between microglial activation and LPS-induced depressive-like behaviors in dams. Collectively, the findings of this study confirm that brief PS from offspring promotes resilience to LPS immune challenge-induced behavioral deficits and inhibits neuroinflammation in dams separated from their offspring during lactation.     

Maternal obesity in the rat programs male offspring exploratory, learning and motivation behavior: prevention by dietary intervention pre-gestation or in gestation

We studied the effects of maternal high fat diet (HFD, 25% calories from fat administered before and during pregnancy and lactation) and dietary intervention (switching dams from HFD to control diet) at different periconceptional periods on male offspring anxiety related behavior, exploration, learning, and motivation. From weaning at postnatal day (PND) 21, female subjects produced to be the mothers in the study received either control diet (CTR - 5% calories from fat), HFD through pregnancy and lactation (MO), HFD during PNDs 21-90 followed by CTR diet (pre-gestation (PG) intervention) or HFD from PND 21 to 120 followed by CTR diet (gestation and lactation (G) intervention) and bred at PND 120. At 19 days of gestation maternal serum corticosterone was increased in MO and the PG and G dams showed partial recovery with intermediate levels. In offspring, no effects were found in the elevated plus maze test. In the open field test, MO and G offspring showed increase zone entries, displaying less thigmotaxis; PG offspring showed partial recuperation of this behavior. During initial operant conditioning MO, PG and G offspring displayed decreased approach behavior with subsequent learning impairment during the acquisition of FR-1 and FR-5 operant conditioning for sucrose reinforcement. Motivation during the progressive ratio test increased in MO offspring; PG and G intervention recuperated this behavior. We conclude that dietary intervention can reverse negative effects of maternal HFD and offspring outcomes are potentially due to elevated maternal corticosterone.     

Overt and hidden forms of chronic malnutrition in the rat and their relevance to man

We have examined the physiological weight changes seen in rat dams and their offspring as sequelae of either an overt or a hidden form of chronic protein malnutrition. In the overt model, which was produced by feeding dams a very low protein diet (6% casein) starting 5 weeks prior to conception and continued through lactation, the females showed significant weight losses at all ages compared to dams maintained on a normal diet (25% casein). This caused the malnourished 6% dams to have offspring that were categorized as small-for-date at birth in terms of their weight indices and peripheral metabolic profiles. Also, the inadequate milk production of these dams resulted in their pups displaying the almost total failure of growth (greater than 60% decreases in body weights) and peripheral imbalances characteristic of infantile marasmus by day 8 of lactation. Consequently, at all times examined the 6% dams and pups showed most of the typical responses seen in the more severe forms of in utero and lactational malnutrition of mankind. In contrast, the hidden form of malnutrition produced by feeding dams a somewhat higher protein diet (8% casein) throughout the same time periods caused no marked weight losses by these females during their pregnancy compared to the normal dams. Although the 8% pups had the same birth weight indices as the normal offspring, previous data from our group have indicated that the 8% progeny show many metabolic imbalances at birth which are indicators of severe gestational malnutrition in humans. Moreover, while the 8% dams displayed lactational insufficiencies as noted by their pups retarded postnatal growth, nursing of these offspring by 25% dams allowed them to maintain a normal lactational growth curve. However, not only was this cross-fostering unable to rehabilitate most of the prenatally determined biochemical alterations affecting the 8% pups but, additionally, this form of malnutrition will remain undetected if weight indices alone are used as assessors of normalcy. Thus, it appears that the 8% rats may serve as a useful model for the hidden forms of malnutrition in man.     

Maternal exposure to bacterial endotoxin during pregnancy enhances amphetamine-induced locomotion and startle responses in adult rat offspring

An increased incidence of schizophrenia has been associated with several perinatal insults, most notably maternal infection during pregnancy and perinatal hypoxia. This study used a rat model to directly test if maternal exposure to bacterial endotoxin (lipopolysaccharide, LPS) during pregnancy alters behaviors relevant to schizophrenia, in offspring at adulthood. The study also tested if postnatal anoxia interacted with gestational LPS exposure to affect behavior. At adulthood, offspring from dams administered LPS on days 18 and 19 of pregnancy showed significantly increased amphetamine-induced locomotion, compared to offspring from saline-treated dams. A period of anoxia on postnatal day 7 had no effect on amphetamine-induced locomotion and there was no interaction between effects of gestational LPS and postnatal anoxia on this behavior. Offspring from LPS-treated dams also showed enhanced acoustic startle responses as adults, compared to offspring from saline-treated dams. In offspring tested for pre-pulse inhibition (PPI) of acoustic startle and for apomorphine modulation of PPI, no effects of either gestational LPS or of postnatal anoxia and no interactions between LPS and anoxia were observed. It is concluded that maternal LPS exposure during pregnancy in the rat may be a useful model to study mechanisms responsible for effects of maternal infection on behaviors relevant to schizophrenia, in offspring.     

Effects of short-term prenatal alcohol exposure on neuronal membrane order in rats

Long-Evans rat dams were treated with ethanol (4 g/kg, twice daily) by gavage on gestational days 10-14. This dosage schedule has been shown to produce significant behavioral and ponderal teratogenicity. Pair-fed dams were gavaged with isocaloric amounts of sucrose. All offspring were reared by untreated, surrogate dams. Pups were sacrificed on days 3 and 28, and whole brain neuronal plasma membranes were prepared for analysis by a fluorescence polarization technique using 1,6-diphenyl-1,3,5-hexatriene as the membrane probe. On day 3, steady-state anisotropy was significantly decreased in the ethanol-treated pups. Arrhenius plots revealed that this difference was associated with a change on both membrane entropy and enthalpy. By day 28, the differences between groups disappeared. These data would be consistent with the view that the brief gestational ethanol exposure delays neuronal maturation.