A fostering study of the effects of prenatal cocaine exposure: II. Offspring behavioral measures

The impact of rearing condition was assessed in Sprague-Dawley dams given 40 mg/kg cocaine (C40) or saline (LC control) subcutaneously (SC) from gestational days 8–20 and their offspring. Treated pups reared by their biological dams (LC/LC; C40/C40), treated pups reared by surrogate dams (FOS/LC; FOS/C40), and foster pups raised by treated dams (LC/FOS; C40/FOS) were examined. On postnatal day 7 (P7), pups received either 0 (unpaired) 2, 3, or 4 pairings of an odor and footshock and were tested for their aversion to this odor. Foster and LC pups, regardless of rearing condition, exhibited significant odor aversions following either 2, 3, or 4 training trials. In contrast, C40 pups reared by surrogate dams required 4 trials to acquire the aversion, and C40 pups reared by their own dams did not exhibit conditioning even after 4 trials. At P17, no differences were seen among the groups in the aversion formed to an auditory or an olfactory stimulus that was paired with footshock. At P60, shock-elicited aggression among pairs of siblings was examined. Regardless of prenatal exposure condition, offspring reared by dams given cocaine showed a decreased latency to the first aggressive contact, an effect that was evident without any alteration in shock sensitivity. Together these data suggest that being reared by a dam previously exposed to cocaine has an impact on offspring behavioral function apart from the effects of prenatal cocaine exposure per se. The implications of the data regarding the cognitive performance of pups exposed prenatally to cocaine are also discussed.     

Responsiveness to cocaine challenge in adult rats following prenatal exposure to cocaine

Adult rats that were gestationally exposed to cocaine and control offspring were examined for their sensitivity to challenge doses of cocaine. Offspring were derived from Sprague-Dawley dams that had received subcutaneous injections of 40 mg/kg per 3 cc cocaine hydrochloride daily on gestational days 8–20, pair-fed dams that were injected with saline, and nontreated control dams. In order to investigate the sensitivity to challenge doses of cocaine, offspring were assessed in adulthood for locomotor activity, cocaine drug discrimination, and the time course of cocaine in brain tissue following acute cocaine challenge. Adult offspring prenatally exposed to cocaine were observed to exhibit a reduced sensitivity to the discriminative stimulus effects of cocaine as evidenced by a significant shift to the right in the dose-response curve of cocaine discrimination. No prenatal treatment effects were observed in terms of the temporal patterns of cocaine discrimination or with regard to brain levels of cocaine. In addition, baseline locomotor activity and locomotor responses to challenge doses of cocaine were comparable across the prenatal treatment groups. Thus, prenatal cocaine exposure reduced sensitivity of offspring to the discriminative stimulus properties of cocaine without altering either the distribution of cocaine to the brain or the sensitivity of the offspring to the locomotor stimulant effects of cocaine.     

Prenatal cocaine exposure attenuates cocaine-induced odor preference in infant rats.

In order to further examine whether prenatal cocaine exposure alters the later reward efficacy of cocaine, exposed offspring were tested for cocaine-induced odor preference early in life. Test offspring were derived from Sprague-Dawley dams that received daily SC injections of 40 mg/kg/3 cc cocaine hydrochloride (C40) from gestational day 8-20, nutritional control dams receiving daily SC saline injections (NC), and nontreated control dams (LC). At testing on postnatal day 8 (P8), both LC and NC offspring were observed to exhibit a preference for the odor that had been paired on P7 with 2.0, 5.0, or 10.0 mg/kg cocaine. In contrast, C40 offspring exhibited a significant odor preference only when the odor had been previously paired with 5.0 or 10.0 mg/kg cocaine. These results, combined with previous work from our laboratory showing that adult offspring exposed gestationally to cocaine did not exhibit a cocaine-induced conditioned place preference, provide evidence that offspring exposed prenatally to cocaine are less likely to develop a preference for stimuli associated with cocaine. Further studies are needed to determine whether these alterations in cocaine preference reflect a learning deficit, pharmacokinetics factors, or an attenuation in the rewarding properties of cocaine.     

Effects of prenatal cocaine on behavioral responses to a cocaine challenge on postnatal day 11.

The purpose of this study was to investigate the effects of prenatal cocaine treatment on behavioral responsivity to a cocaine challenge on postnatal day (PD) 11. Timed-pregnant Sprague-Dawley rats were injected s.c. with 40 mg/kg/day of cocaine (20 mg/kg twice daily) from gestational day 11 to 20. Saline-control females received saline injections and were pair-fed to the cocaine-treated females, whereas untreated-control females were undisturbed and were fed ad lib. Litters were culled to eight pups on PD1 and fostered to normal lactating dams. On PD 11, subjects were given either saline or cocaine (1.25, 2.5, or 5.0 mg/kg s.c.) and then tested 15 min later for isolation-induced ultrasonic vocalizations and other behaviors. Prenatal cocaine-treated pups showed a reduced sensitivity to the stimulating effect of postnatal cocaine on wall climbing, which may reflect an underlying alteration in central dopaminergic and/or noradrenergic systems. Most of the other behaviors studied, including ultrasonic vocalizations, were unaffected by prenatal cocaine administration. However, one other notable finding was an increase in postnatal mortality among the cocaine-exposed pups. We hypothesize that prenatal cocaine treatment may alter pup behavior so as to produce abnormal maternal-offspring interactions and impaired development in some individuals.     

Schedule-induced polydipsia: gender-specific effects and consequences of prenatal cocaine and postnatal handling

The impact of gestational cocaine in conjunction with postnatal handling on schedule-induced polydipsia (SIP) was examined. Rat offspring were derived from Sprague-Dawley dams injected subcutaneously with 40 mg/kg/3 cc cocaine hydrochloride (C40) on gestational days 8-20, dams injected with vehicle and pair fed 4 (PF4) days to mimic the acute anorexic effects of cocaine administration, and nontreated (NT) control dams. In adulthood, offspring were food deprived and given 13 daily 30-min SIP sessions, with water intake recorded during the scheduled (fixed time 60 s-FT60) food delivery. For 4 days thereafter, animals received saline, 5 or 10 mg/kg of cocaine in counterbalanced order prior to SIP testing. Acquisition and maintenance of SIP, but not cocaine-induced suppression of SIP performance, were observed to be dependent upon prenatal treatment, handling, and gender. Females acquired SIP faster and exhibited notably higher levels of polydipsia than males. Early handling increased levels of established SIP in NT offspring, while enhancing SIP acquisition in both PF4 and C40 offspring. In nonhandled animals, NT offspring exhibited less SIP than PF4 and C40 offspring, differences that were attenuated by early handling. These effects are discussed in relation to previously reported neurohormonal characteristics of these gender and treatment variables.     

Prenatal cocaine: maternal toxicity, fetal effects and locomotor activity in rat offspring

Either 30 or 60 mg/kg of cocaine hydrochloride (COC) was administered by gastric intubation to gravid rats during the last two weeks of gestation. A pair-fed control group was administered the vehicle alone and allowed to eat and drink only the amount consumed by the 60 mg/kg group on the same gestation days. A nontreated control group was left undisturbed during pregnancy. All treated and control litters were fostered at birth to untreated dams. None of the treated dams died nor were any gross signs of cocaine toxicity observed. Among the COC-60 dams, there was a reduction in food and water intake at the beginning of treatment; whereas water intake returned to control levels, food intake remained approximately 12% below that of the controls. Compared to the nontreated dams, both COC-treated and pair-fed dams gained significantly less body weight from conception to term. Cocaine had no effect on offspring mortality, birthweight or rate of postnatal growth. Measurement of the ontogeny of motor activity during the first month of life revealed a similar activity pattern for all the groups except for the COC-60 group which showed heightened activity on Days 20 and 23. These findings are discussed in relation to other animal and clinical reports of prenatal cocaine exposure.     

Cocaine and development: a retrospective perspective

Neurobehavioral alterations evident in offspring of Sprague-Dawley rat dams exposed to 40 mg/kg/day cocaine subcutaneously from gestational days 8-20 are reviewed. Consequences for offspring are often age dependent: for instance, reliable deficits in classical conditioning are evident during the early postnatal period, whereas cognitive effects are less pervasive in adulthood, although apparent in tasks such as reversal training. Gender of offspring is another variable of importance, particularly when testing animals in adulthood, with adult male offspring being more likely than their female counterparts to exhibit alterations following the prenatal exposure regimen. Characteristics of the test situation likewise influence detection of outcome effects, with effects particularly likely to emerge under stressful testing conditions or other challenges to the organism. Under these circumstances, alterations in responsiveness to stressors also sometimes emerged in offspring of pair-fed (PF) dams (whose food intake was restricted to match that of cocaine-exposed [COC] dams); these findings perhaps should not be surprising given that pair feeding is a stressor and prenatal stress is known to alter later stressor responsiveness. Although several approaches to equate food intake or avoid pair feeding have yielded disappointing findings, one promising approach is to initiate cocaine administration prior to mating followed by exposure throughout gestation. Premating exposure to cocaine was sufficient to eliminate anorexic effects of drug delivery during pregnancy, although it remains to be seen how similar the pattern of neurobehavioral alterations that emerge with this extended exposure regimen will be to effects seen following more restricted gestational exposure.     

Effects of prenatal cocaine on behavioral adaptation to chronic stress in adult rats

Prenatal exposure to cocaine in rats has previously been shown to alter the behavioral and hormonal responses to acute stressors, although no work has yet examined stress adaptation in these animals in adulthood, a possibility examined in this experiment. Male and female offspring of Sprague–Dawley rat dams given 40 mg/kg/3 ml subcutaneously daily from gestational days 8–20 (C40), saline injected and pair-fed dams (PF), and non-treated dams (NT) were tested in adulthood (90–120 days). Offspring were given a 5-min open field test 24 h following the last of 1 (Acute), 9 (Chronic) or 0 (control) daily 15-min intermittent footshock sessions. Substantially more behavioral adaptation was evident in NT offspring than in C40 and PF animals. The attenuated stress adaptation seen in C40 offspring extends prior work showing altered stress responsiveness in these animals, although the PF data caution against the conclusion that this lack of stress adaptation necessarily reflects gestational exposure to cocaine per se.     

Behavioral and developmental effects in suckling mice following maternal exposure to the mycotoxin secalonic acid D

Pregnant mice (dams) were gavaged once on gestational day 13 with 4 ml/kg of dimethylsulfoxide vehicle containing 0 (groups 15, 25 and negative control) or 25 (positive behavioral teratogenic control group) mg/kg of secalonic acid D (SAD). While nursing their offspring, dams were gavaged on postgestational days 1 to 10 with vehicle containing 0 (negative and positive control groups), 15 (group 15) or 25 (group 25) mg/kg/day of SAD. Gestational lengths, maternal pregnancy weights, litter sizes, neonatal sex ratios, neonatal physical appearance and female birth weights were unaffected by prenatal treatment, but male pups born to positive control dams weighed less (p less than 0.05) than negative control group. Compared to negative control, the positive control dams gained significantly more weight while nursing their offspring. Prenatal (positive control) and postnatal (15, 25) SAD exposure delayed ontogeny of surface righting, olfactory discrimination and hindlimb grip behaviors in males and females, and testes descent in males. Negative geotaxis in male and female offspring of group 25 and male offspring of positive control group, as well as times of incisor eruptions of both sexes in groups 15 and 25 were delayed. A significant dose-response effect in olfactory discrimination existed between the groups exposed to postnatal SAD. SAD was behaviorally teratogenic following both prenatal and early postnatal exposure.     

Prenatal cocaine effects on fear conditioning: exaggeration of sex-dependent context extinction

Prenatal cocaine exposure results in deficits in sensory preconditioning, discrimination reversal, and spatial navigation, tasks that require input from the hippocampus. However, there are no previous studies concerning prenatal cocaine effects on contextual fear conditioning, another hippocampal-dependent task. The present experiments tested whether chronic subcutaneous administration of 40 mg/kg of cocaine HCl to pregnant rats, from gestational day (GD) 8 through 20 would lead to disruption of contextual fear conditioning in adult male and female offspring. Offspring of saline-injected/pair-fed and untreated dams served as controls. Experiment 1 used a one-trial context conditioning preparation. Rats received a 2-s, 1-mA footshock in either the test context or a novel context, or received no shock on the day prior to the no-shock test. Defecation and freezing were measures of fear. Experiment 2 used a multiple measures protocol to optimize detection of prenatal treatment effects and was preceded by an open-field test. Rats received a 2-s, 0.8-mA footshock or no shock once daily over 4 days of conditioning. During 3 days of extinction, access to an adjacent chamber enabled the observation of four additional measures of fear: side crossing, latency, nose crossing, and side-differential. There were gender-dependent effects of conditioning on freezing and the four added measures of fear. Males showed higher levels of context conditioning and extinguished more slowly than females. The measures of nose crossing and side-differential revealed that prenatal cocaine exposure exaggerated gender-specific effects of context conditioning. The effects of prenatal cocaine exposure on context extinction are sexually dimorphic.     

Locomotor behavioral effects of prenatal and postnatal nicotine exposure in rat offspring

The purpose of this study was to determine if prenatal/postnatal nicotine exposure results in hyperactive offspring. Rat offspring were exposed to nicotine, through implantation of osmotic minipumps in dams, at levels of 0.75, 1.5 and 3.0 mg/kg/day, for 19 days prenatally and 16 days postnatally. Offspring were measured for gestation length, body weight, litter size, sex difference and locomotor activity. No significant effects were shown for gestation length, litter size or male to female pup ratio. However, higher percentage of pup deaths resulted from nicotine-exposed dams than from control dams. Significantly less litter body weight was shown in nicotine-exposed offspring on postnatal day 1 when compared to controls. However, these offspring surpassed the control groups in litter body weight on postnatal day 14 and 21. Hyperactivity was shown in offspring exposed to prenatal/postnatal nicotine at levels of 0.75 and 3.0 mg/kg/day on postnatal day 14, but not on postnatal day 21 or at the 1.5 mg/kg/day condition. Results are consistent with the hypothesis that rat offspring are susceptible to the neurochemical and neurobehavioral effects of prenatal/postnatal nicotine exposure.     

Exploratory behavior and locomotor activity: a failure to find effects in animals prenatally exposed to cocaine.

Pregnant Long-Evans rats were administered cocaine orally (60 mg/kg) on gestational days 14-21, or subcutaneously (40 mg/kg) on gestational days 8-21. The oral dosage of cocaine produced some maternal lethality and reduced maternal weight gain throughout the pregnancy by approximately 12%. The subcutaneous dosage regimen reduced the lethality but still caused a decrease in maternal weight gain. Neither dosing regimen affected the number of pups in the litter, their weight, or growth. The offspring of dams that received the oral dosage were examined as adults in an automated holeboard apparatus and were also tested at postnatal day 21 and as adults in an open field. Adult animals exposed prenatally to cocaine did not differ from untreated controls in any of the automated measures of the holeboard apparatus or in the various behaviors, including nosepokes, recorded in the open field. Animals in the vehicle control group did make fewer nosepokes in the open field than the cocaine group, which did not differ from untreated animals. The offspring of dams given the subcutaneous dosage regimen were observed in the open field at day 21. In this case, the prenatal cocaine group had a tendency to make fewer crosses into adjacent quadrants, to rear less often, and to make fewer nosepokes than the control groups. Based on these and other data from our lab, it does not appear that in the rat, prenatal cocaine exposure has pronounced effects on subsequent exploratory behavior and activity in weanling or adult animals.     

Interactive effects of prenatal alcohol and cocaine exposures on postnatal mortality, development and behavior in the Long-Evans rat

Polydrug abuse has increased substantially in recent years amongst obstetric patients. One of the most common drug combinations is alcohol and cocaine. To better understand the adverse consequences of this drug combination on pregnancy and the offspring, alcohol (2 g/kg, b.i.d.) and cocaine HCl (30 mg/kg, b.i.d.) were administered individually and in combination to separate groups of pregnant Long-Evans rats from gestation days 7-20. The pregnant dams were evaluated for maternal weight gain, food and water consumption, mortality, and gestational length. The offspring were evaluated for physical maturation, mortality, and behavior. The drug combination was found to have greater effects regarding decreased birth weight, increased postnatal mortality, and delayed physical maturation than either drug alone. Drug treatments also influenced activity monitor behavior in that prenatal cocaine exposure was associated with hypoactivity while the alcohol and the alcohol-plus-cocaine treatments were associated with hyperactivity in periweanling pups. Drug treatments had no significant effects on passive or active avoidance behaviors. These results suggest that combining alcohol and cocaine increases the risk to the offspring.     

Prenatal exposure to cocaine disrupts cocaine-induced conditioned place preference in rats.

Cocaine-induced conditioned place preference (CPP) was tested in adult offspring of Sprague-Dawley dams that had been injected subcutaneously with 40 mg/kg/3cc cocaine HCl (C40) daily from gestational days 8-20, pair-fed (PF) dams injected with saline, and nontreated control (LC) dams. C40 and PF dams gained significantly less weight than LC dams, although offspring body weights did not differ among the three prenatal treatment groups at birth or in adulthood. Significant place conditioning was obtained in LC and PF offspring when either 2.0 or 5.0 mg/kg of cocaine was paired with the designated place. In contrast, C40 offspring did not exhibit place conditioning at either training dose. Yet, all animals exposed to 5 mg/kg of cocaine during conditioning exhibited less activity during the test (when no cocaine was given) than controls given unpaired exposures to the apparatus and cocaine and C40 offspring did not differ from LC and PF offspring in this respect. Therefore, despite their lack of a conditioned place preference for cocaine, rats that had been exposed gestationally to cocaine nevertheless revealed an effect of cocaine during conditioning in one aspect of their test behavior. Possible explanations for the lack of cocaine-induced place preference in these animals include a learning deficit or a change in cocaine's effectiveness as a reward.     

The effect of prenatal methadone exposure on development and nociception during the early postnatal period of the rat

The effects of prenatal exposure to methadone via Alzet osmotic minipump on early postnatal development and on nociceptive behavioral endpoints were assessed in Sprague-Dawley rat pups during the first three postnatal weeks. This treatment regimen appeared to produce no maternal toxicity, with dams developing and maintaining dependence upon methadone through parturition. Methadone-exposed dams exhibited a withdrawal syndrome consisting of wet-dog shakes, diarrhea, vocalizations and irritability when challenged with naloxone 24 h postpartum. Pups exhibited a similar withdrawal syndrome following naloxone challenge consisting of mouthing and licking, hyperactive response to touch and vocalizations 24 h postpartum. Although no significant difference in litter size was evident in methadone-treated litters, a 16% pup mortality rate was observed in these litters. Prenatal methadone-exposed pups exhibited a significant body weight reduction at birth that resolved by postnatal day 2 (P2) in males and P4 in females. Methadone-exposed pups exhibited significant developmental delay in the expression of the negative geotaxic response to a morphine challenge while, conversely, 21-day-old pups exhibited a significantly reduced analgesic response to this challenge. These studies indicate that this method of prenatal exposure to methadone can produce dependence in the dam and offspring without substantial mortality, induce developmental delay and alter analgesic responses to opiate challenge in exposed pups during the preweanling period.     

Effects of prenatal phencyclidine on 3H-PCP binding and PCP-induced motor activity and ataxia

Either phencyclidine hydrochloride (PCP) (5, 10, or 20 mg/kg) or saline was administered by subcutaneous injection to gravid CF-1 mice during either Mid (E6-15) or Late (E12-18) gestation. A nontreated control group (UTC) was left undisturbed during pregnancy. All treated and control litters were fostered at birth to untreated dams. Although postnatal challenge of PCP increased motor activity and ataxia in a dose-related manner, prenatal PCP had no effect on postnatal motor activity, ataxia or 3H-PCP binding. However, treatment period did have a significant effect on ataxia and 3H-PCP binding. In response to challenge doses of 5.0 and 7.5 mg/kg PCP, ataxia scores of the Late gestation offspring were significantly greater than the UTC offspring which in turn were significantly greater than the ataxia scores of the Mid gestation group. The results are discussed in relation to other animal and clinical reports of prenatal PCP exposure.     

Prenatal cocaine alters dopamine and sigma receptor binding in nucleus accumbens and striatum in dams and adolescent offspring

Maternal cocaine abuse is a societal problem with serious impact on both mother and child. Few studies exist that study the mother/offspring dyad of neurological effects of maternal cocaine abuse. The present study was designed to study alterations in D2, D3 and sigma receptor density in nucleus accumbens and striatum of dams and male and female offspring following gestational cocaine. Long-Evans female rats were implanted with an intravenous (i.v.) access port prior to breeding and were administered saline or 3.0 mg/kg of cocaine from gestational day (GD) GD8-20 (1 injection/day-GD8-14, 2 injections/day-GD15-20). Offspring were raised by maternal dams and allowed to mature until postnatal days 31-35, at which time dams and offspring were sacrificed for assay of radioligand binding. In dams, decreased D2 (24.6%) and D3 (36.9%) binding was observed in striatum. Female offspring displayed no differences in receptor binding in either region. Male offspring displayed decreased D2 receptor binding (27.1%) in nucleus accumbens and increased D3 (75.2% and 33.5%) and sigma receptor binding (73.4% and 53.1%) in accumbens and striatum, respectively. Collectively, these data clearly demonstrate that male offspring exhibit significant alterations in D2, D3 and sigma receptor binding. These results suggest that dams and offspring display long-lasting alterations (5 weeks) in dopamine receptor binding. These alterations in dopamine and sigma receptor binding in offspring following prenatal cocaine and rearing by maternal dams are sex specific and could have profound effects on the development of behavior.     

Attenuation of cocaine-induced genomic and functional responses in prenatal cocaine-exposed rabbits.

The effects of in utero cocaine exposure on cocaine-induced genomic and functional responses in postnatal life were examined. Pregnant Dutch Belted rabbits were injected intravenously, twice daily, with cocaine hydrochloride (4 mg/kg) or saline from day 8 through day 29 of pregnancy. Prenatally exposed kits were challenged with cocaine on postnatal day 20. In prenatal saline-exposed kits, cocaine induced time- and dose-dependent c-fos gene expression in both frontal cortex and striatum. Prenatal cocaine exposure reduced cocaine-induced c-fos responses by 35-58% in the frontal cortex and 37-41% in the striatum. Cocaine-induced functional responses that included head bobbing, seizure, and locomotor activity were also attenuated in prenatal cocaine-exposed kits. Cocaine-induced c-fos expression and functional responses were blocked by the D(1) dopamine receptor antagonist, SCH23390, or by the serotonin receptor antagonist, methysergide, but not by the D(2) dopamine receptor antagonist, L-sulpride. The results indicate that in utero cocaine exposure leads to diminished responses to cocaine challenge in the offspring, which may be mediated by prenatal cocaine-induced alterations in one or more components of the D(1) dopamine and/or serotonin receptor signaling systems during early postnatal life.     

Behavioral effects of prenatal haloperidol exposure

Pregnant albino rats were exposed to vehicle (CON), 2.5 mg/kg (LOW) or 5.0 mg/kg (HIGH) haloperidol (HAL) from the sixth through the twentieth day of gestation. The effect of prenatal HAL exposure on offspring was assessed with the following five behavioral measures: 1) milk-induced behavioral activation on the sixth postnatal day (PND 6), 2) shock-precipitated wall climbing (PNDs 9, 11, 13, 15 and 17), 3) amphetamine-induced stereotypies (PND 30), 4) apomorphine-induced stereotypies (PND 30) and 5) duration of barbiturate anesthesia (PNDs 34 and 62). Measures taken very early in life indicated that prenatal HAL reduced arousal. Inactivity scores were elevated in HAL-exposed pups on PND 6 during milk-induced behavioral activation. Shock-precipitated wall climbing was reduced in the HAL animals on PNDs 9 and 11, but not thereafter. At PND 30, no prenatal treatment effect was detectable on stimulant-induced stereotypies or on duration of barbiturate anesthesia. On PND 62, barbiturate anesthesia duration was significantly reduced in both sexes of HIGH HAL animals. These findings suggest that prenatal HAL effects follow a dynamic, changing course as the exposed rat pup matures. Early reductions in arousal (milk-induced behavior and shock-precipitated wall climbing) wane with age, perhaps to be replaced by an actual increase in arousal as HAL pups approach adulthood.     

Fertility and developmental neurotoxicity effects of inhaled hydrogen sulfide in Sprague-Dawley rats

In this study, we examined whether perinatal exposure by inhalation to hydrogen sulfide (H2S) had an adverse impact on pregnancy outcomes, offspring prenatal and postnatal development, or offspring behavior. Virgin male and female Sprague-Dawley rats (12 rats/sex/concentration) were exposed (0, 10, 30, or 80 ppm H2S; 6 h/day, 7 days/week) for 2 weeks prior to breeding. Exposures continued during a 2-week mating period (evidence of copulation = gestation day 0 = GD 0) and then from GD 0 through GD 19. Exposure of dams and their pups (eight rats/litter after culling) resumed between postnatal day (PND) 5 and 18. Adult male rats were exposed for 70 consecutive days. Offspring were evaluated using motor activity (PND 13, 17, 21, and 60+/-2), passive avoidance (PND 22+/-1 and 62+/-3), functional observation battery (PND 60+/-2), acoustic startle response (PND 21 and 62+/-3), and neuropathology (PND 23+/-2 and 61+/-2). There were no deaths and no adverse physical signs observed in F0 male or female rats during the study. A statistically significant decrease in feed consumption was observed in F0 male rats from the 80-ppm H2S exposure group during the first week of exposure. There were no statistically significant effects on the reproductive performance of the F0 rats as assessed by the number of females with live pups, litter size, average length of gestation, and the average number of implants per pregnant female. Exposure to H2S did not affect pup growth, development, or performance on any of the behavioral tests. The results of our study suggest that H2S is neither a reproductive toxicant nor a behavioral developmental neurotoxicant in the rat at occupationally relevant exposure concentrations (< or =10 ppm).