Requirement for Brn-3b in early differentiation of postmitotic retinal ganglion cell precursors

Postnatal development of the spinal cord serotonergic (5-HT) system and of swimming movements were studied in newborn Sprague-Dawley rats, in which the serotonin level in the central nervous system was lowered in the prenatal period. For this purpose, para-chlorophenylalanine (PCPA) (300 mg/kg) was administered intraperitoneally to pregnant mother rats on day 8 of gestation, followed by a daily injection of PCPA (80 mg/kg) from day 9 of gestation to delivery. The postnatal development of the 5-HT system in the spinal cord of the pups (PCPA-treated pups) born from the PCPA-administered mothers was markedly delayed during the period between PND 1 and PND 10 in comparison to that in the control pups born from healthy mothers. Postnatally, the control pups developed their swimming movements regularly through three distinct phases: forelimb dominant, forelimb and hindlimb well coordinated, hindlimb dominant. In contrast, in the PCPA-treated pups, swimming movements were disorganized during the period in which the development of 5-HT system was delayed. However, between PND 17 and 22 in which the 5-HT system developed to that extent observed in the control pups, the pups eventually developed swimming movements as observed in the control pups. These results suggest that the disorganized developmental process of swimming movements in the PCPA-treated pups is due to the possible failure in the prenatal and postnatal development of the 5-HT system and its target system in the brain stem and the spinal cord.     

Chronic neonatal nicotine increases anxiety but does not impair cognition in adult rats.

Developmental nicotine exposure has been implicated in the association between maternal smoking and adverse outcomes in offspring. The 3rd trimester of human pregnancy is equivalent to the 1st postnatal week in rodents; both are periods of active brain growth during which nicotinic acetylcholine receptors are transiently upregulated. Chronic neonatal nicotine (CNN; 6 mg/kg/day) from postnatal Days 1 to 7 was given orally to rat pups to evaluate long-term behavioral effects. Males and females were tested as adolescents or as young adults. CNN significantly decreased center time, ambulatory behavior, and rearing in the open-field test and decreased the number of entrances and time spent in the open arm of the elevated plus-maze in both sexes and ages. CNN did not change performance in the T maze or in the water maze in adult males or females. Motor coordination was not altered. In summary, CNN had long-term effects on anxiety-like behavior but did not affect spatial learning and memory functions. This finding is particularly important when evaluating the benefits of nicotine-replacement therapies during human pregnancies, which may improve smoking cessation rates but could result in long-term behavioral consequences. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Gestational retinoic acid exposure: a sensitive period for effects on neonatal mortality and cerebellar development

This is the first in a series of studies investigating the developmental stage-specific neurobehavioral effects of all-trans retinoic acid (RA) exposure. Because high doses of this compound are known to be lethal to the developing organism, we first conducted a dose-response study to identify RA doses that produce low enough levels of gestational/postnatal mortality to make a behavioral analysis possible in survivors. Secondarily, at doses found to produce sufficient survivors on PND 28, effects on body and regional brain weights were examined. Finally, at these doses, effects on somatic malformations were evaluated. Four separate exposure periods were analyzed: gestational days (GD) 8 through 10, 11 through 13, 14 through 16, or postnatal days (PND) 3 through 5. In the postnatal exposure period rat pups were injected (s.c.) with three consecutive daily doses of 0, 5, 10, or 20 mg/kg RA on PND 3 through 5. This postnatal exposure had no detectable effect on survival, body or brain weight. In contrast, there was a marked sensitivity to RA in the GD 11-13 group. Many pups from dams given 10 mg/kg RA PO on GD 11-13 were found dead in the cage on the day of birth, and all surviving pups died within 4 days of birth. Examination of milkbands revealed no evidence of effective suckling in these short-term survivors. The same 10 mg/kg dose at GD 8-10 or GD 14-16 produced much lower mortality and pups appeared to suckle normally. To produce adequate PND 28 survival in the GD 11-13 group, it was necessary to reduce dosage to 2.5 mg/kg daily. Even this lower exposure produced effects on PND 28 body and brain weight, significantly lowering weights of body (84% of control), whole brain (94%), and cerebellum (90%). Cerebellar weight was also depressed as percent of whole brain weight, suggesting an effect focused specifically on this region. RA at 10 or 12.5 mg/kg over GD 14-16 also reduced cerebellar weight (92% and 91% of control, respectively). Thus, exposure on GD 14-16 had effects similar to those seen at GD 11-13, but only at considerably higher doses. In contrast, exposure to RA on GD 8-10 did not affect whole body or brain weight, and of eight brain regions examined, only brain stem weight was reduced (91% of control). The GD 8-10 exposure also differed substantially from later exposures in that it was the only treatment to produce substantial malformations, including exencephaly, eye and skeletal defects. We conclude that gestational exposure to RA produces lethality and regional brain stunting that is dose and developmental stage specific, with a pronounced sensitive period on GD 11-13. In contrast, the GD 8-10 period is most sensitive for production of malformations, albeit at somewhat higher doses.     

D-cycloserine, a partial NMDA receptor-associated glycine-B site agonist, enhances reversal learning, but a cholinesterase inhibitor and nicotine has no effect

The present study examined the efficacy of single and combined treatments with an anticholinesterase, tetrahydroaminoacridine, nicotine and a glycine-B site partial agonist, D-cycloserine, in alleviating the water maze reversal learning defect induced by a medial septal lesion. D-cycloserine (3 and 10 mg/kg) improved reversal learning. Tetrahydroaminoacridine (1 and 3 mg/kg) and nicotine (0.1 and 0.3 mg/kg) had no effect on reversal learning. A combination of tetrahydroaminoacridine 3 mg/kg or nicotine 0.3 mg/kg and D-cycloserine 10 mg/kg was not more effective than D-cycloserine 10 mg/kg alone in improving reversal learning. This suggests that stimulation of NMDA mechanisms may more effectively improve in medial septal-lesioned rats reversal learning processes than stimulation of cholinergic activity.     

Interactions of gonadal steroids and pesticides (DDT, DDE) on gonaduct growth in larval tiger salamanders, Ambystoma tigrinum

The nervous system is dependent upon thyroid hormones for normal development, and we previously reported that developmental Aroclor 1254 (A1254) exposure caused hypothyroxinemia, hearing loss and other behavioral changes in rats. (Goldey et al., 1995a; Herr et al., 1996). The hypothesis that A1254-induced hypothyroxinemia may have contributed to the observed functional changes was tested in primiparous Long-Evans rats given daily oral doses of corn oil (control) or 8 mg/kg of Aroclor 1254 from gestation day (GD) 6 through postnatal day (PND) 21. In addition, from PND 4 to PND 21, all pups in one-half of the litters received daily, subcutaneous injections of saline or 100 micrograms/kg thyroxine (T4), to yield four groups of litters: corn oil plus saline (CO-S),. corn oil plus T4 (CO-T4), Aroclor 1254 plus saline (PCB-S), and Aroclor 1254 plus T4 (PCB-T4). We measured thyroid hormone concentrations (T4 and T3) in serum collected from 7-, 14-, and 21-day-old pups. The kinetics of the injected T4 were also monitored in the CO-T4 and PCB-T4 groups on PND 7 and 21 by measuring T4 and T3 at 1, 3, 5, 8, and 24 h after injection. Circulating T4 concentrations were dramatically depleted in the PCB-S group relative to CO-S. The kinetics study indicated that T4 therapy raised circulating T4 concentrations following in the PCB-T4 pups to near CO-S concentrations, but only for approximately 6 h postinjection, and T4 concentrations fell precipitously thereafter to near PCB-S concentrations. In accord with previous studies, PCB-S pups showed early eye opening, an effect which was exacerbated by T4 injection (in both the CO-T4 and the PCB-T4 groups). Motor activity (figure-eight maze) testing also replicated our finding of an age-dependent, transient reduction in motor activity on PND 15 that was significantly attenuated in the PCB-T4 group. Similarly, we again found reduced acoustic startle amplitudes on PND 23 and low-frequency (1 kHz) hearing loss in animals tested as adults (the latter determined by reflex modification audiometry). Importantly, the hearing loss at 1 kHz in PCB-exposed animals was significantly attenuated by T4 replacement therapy. These data suggest the hypothesis that hypothyroxinemia is involved in PCB-induced alterations in motor and auditory function, while other effects (e.g., eye opening) appear to have a different mechanism of action.     

Conditioned flavour preference negatively reinforced by caffeine in human volunteers

This study examined the effects of neonatal cocaine exposure on responsivity to the alpha2 noradrenergic agonist clonidine in 11-day-old rat pups. On postnatal day (PND) 4 neonatal rats were assigned to one of four treatment groups: artificially reared (AR) receiving 40 mg/kg/day cocaine hydrochloride, AR receiving 20 mg/kg cocaine, AR control receiving no drug, and a normally reared control group. Pups were maintained in this fashion from PND 4 to 9 and received no drug on PND 10. On PND 11 subjects received an IP injection of either 0, 0.25, or 1.0 mg/kg clonidine hydrochloride and were observed for locomotor activity and wall-climbing during a 15-min test session. Subjects exposed to the 40 mg/kg dose of cocaine demonstrated an enhanced sensitivity to the locomotor stimulating effects of clonidine relative to both control groups. This cocaine-related enhanced sensitivity was not observed on the wall-climbing measure. All groups showed evidence of wall-climbing, although this behavior was somewhat dampened among AR groups. The 20 mg/kg cocaine-exposed males also took longer to display wall-climbing behavior than their respective females regardless of clonidine dose, although this sex difference was not apparent for any other treatment group. These findings suggest that neonatal cocaine exposure may alter response of the noradrenergic system.     

Prenatal fumonisin (FB1) treatment in rats results in minimal maternal or offspring toxicity

To investigate the neurobehavioral and developmental effects of the mycotoxin, FB1, Sprague-Dawley rats were treated with FB1 on gestational days 13-20. In Experiment 1, FB1 was obtained from culture material and pregnant rats were gavaged with 0, 0.8 or 1.6 mg/kg. In Experiment 2, pregnant rats were gavaged with purified FB1 at doses of 0, 1.6 or 9.6 mg/kg. Offspring were evaluated on a battery of behavioral tests as well as measures of whole and regional brain weight. There were no effects on maternal weight gain, reproductive outcomes, or offspring body weight through adulthood in either experiment. Complex maze performance, open field and running wheel activity were not altered by prenatal FB1 treatment. In Experiment 2, acoustic startle response was depressed at two ages during the first or second block of 9 trials in males treated with purified FB1. Females exhibited no such alterations. Play behavior at PND 33, but not PND 26, was increased in males prenatally treated with 9.6 mg/kg relative to those treated with 1.6 mg/kg. There were no substantive treatment effects on regional brain weight. These results suggest that doses of < or = 9.6 mg purified FB1/kg and/or < or = 1.6 mg FB1/kg obtained from culture material cause minimal maternal toxicity and produce few development functional alterations. In addition, potential FB1-related functional alterations were evident only in males providing further support for a mild sex-specific effect for fumonisin.     

Neurochemical and neurobehavioral effects of repeated gestational exposure to chlorpyrifos in maternal and developing rats

Acute exposure to the organophosphate pesticide chlorpyrifos (CPF) on gestation day 12 (GD12, 200 mg/kg/ml, SC) causes extensive neurochemical changes in maternal brain but lesser changes in fetal brain. In the present study, we examined the relative neurotoxicity of repeated, lower-level CPF exposures during gestation in rats. Pregnant Sprague-Dawley rats were exposed to CPF (6.25, 12.5, or 25 mg/kg per day, SC) from GD12-19 and sampled at either GD16, GD20, or postnatal day 3 (PND3) for measurement of various maternal and developmental neurochemical markers. In contrast to the high acute dose exposure, no maternal toxicity was noted with repeated lower-level dosing. Extensive acetylcholinesterase (AChE) inhibition (83-90%) was noted in maternal brain at all three time points following repeated exposures (25 mg/kg). Higher AChE inhibition (58%) was noted in fetal brain at GD20 compared to 19-25% on PND3 in treated pups cross-fostered to control dams and in control pups cross-fostered to treated dams following repeated exposures (25 mg/kg per day). Whereas similar reductions in brain muscarinic receptor binding were noted at GD20 and PND3 in dams and developing brain between acute and repeated dosing regimens, greater changes in [3H]CD and [3H]cytisine binding were evident following repeated exposures. Righting reflex and cliff avoidance tests were markedly altered following repeated exposures. The results suggest that lower-level repeated exposures to CPF cause extensive neurochemical and neurobehavioral changes in developing rats in the absence of maternal toxicity.     

Immediate and long-term effects of neonatal MK-801 treatment on nonspatial learning

These experiments observed the immediate and long-term effects of neonatal treatment with MK-801 on patterned single alternation (PSA), a form of nonspatial, memory-based learning. Rat pups were injected daily on postnatal days (PND) 7-19, with MK-801 (MK+) or the less active isomer of MK-801 (MK-) (0.25 mg/kg), and trained at either PND 22 or 60. Rats treated with MK+ or MK- and trained on PND 22 were significantly impaired in PSA when compared with the saline control. Beyond the learning impairment, MK+ rats showed an overall decreased running speed during training. They also presented an array of abnormal behaviors and significant weight loss. These nonassociative variables were determined for several doses (0.025, 0. 05, 0.1, 0.15, and 0.20 mg/kg) through PND days 22-25. Rats that received the threshold dose for secondary effects (0.025 mg/kg) also showed an overall decrease in running speed, but failed to show a significant nonspatial learning impairment on PSA. The PSA learning impairment was found to be not long lasting; rats trained at PND 60, after neonatally receiving the original high dose of MK-801, did not differ from controls.     

Postnatal NGF administration causes adult hyperalgesia and overreactivity to social stimuli but does not reverse capsaicin induced hypoalgesia

The present longitudinal analysis was aimed at assessing (i) the effects of developmental capsaicin (CAPS) administration on nociceptive responsivity and on the response of adult mice to social stimuli; (ii) the action of NGF on the ontogeny of the same nociceptive response and social stimuli; (iii) whether capsaicin treatment could be reversed by subsequent treatment with NGF. CD-1 mouse pups were treated with either capsaicin (50 mg/kg, s.c.) or vehicle on postnatal days (PNDs) 5 and 8. Every other day from PND 9 to PND 21 the same pups received a daily injection of NGF (0.75 mg/kg, s.c.). During both the prepuberal stage (PNDs 14, 21, and 28) and adulthood, mice were repeatedly tested in a hot-plate apparatus (52 +/- 0.1 degrees C for 1 min). At adulthood they also underwent an aggressive behaviour test. NGF-treated mice showed a shorter latency to hindlimb licking response in the hot plate compared to both controls and NGF-CAPS groups. CAPS-treated subjects showed a long-lasting hypoalgesia at both prepuberal and adult stages that was not modified by subsequent NGF treatment. Finally, NGF-treated mice were more aggressive than both controls and CAPS-NGF animals.     

Intravenous gestational cocaine in rats: effects on offspring development and weanling behavior

Pregnant rats were injected with cocaine (CN; 6 mg/kg) or an equal volume of saline (SAL), via the tail vein, on gestation days 8-20. A third group was untreated (UT). Maternal weight gain was not affected by dam treatment despite slight differences in food intake. Litter characteristics (e.g., litter size, pup weight) did not differ among groups. Indices of fetal mortality were not affected by the treatments. Developmental tests, initiated on postnatal day (PND) 2, indicated slight delays in the negative geotaxic response and eye opening in cocaine-exposed pups. Open-field and tail-flick tests were performed on PND 21. Pups were acutely injected with cocaine (10 mg/kg, IP), saline, or received no treatment before placement in a novel open field; morphine (1.5 mg/kg, SC) or saline was injected prior to the tail flick test. Pups from CN dams exhibited a significant decrease in spontaneous exploratory behavior compared to both controls, and a time-dependent increase in rearing compared to pups from UT dams. The acute cocaine injection prior to placement in the open field did not alter locomotion or rearing among dam treatment groups. However, the acute cocaine injection did increase stereotypy ratings for female pups from CN dams compared to similarly treated males, and females from SAL and UT dams. No differences were observed among groups in the tail-flick test. These data suggest that the IV route of administration provides a viable method of cocaine delivery in pregnant rats, and provides further evidence of the developmental and behavioral teratogenicity of prenatal cocaine exposure.     

Surgical treatment of morbus Menière (author''s transl)

CFW mice were injected with methylmercury hydroxide (1, 2, 3, 5 or 10 mg/kg as mercury) on Day 8 of gestation. Mice treated with 3, 5 or 10 mg/kg averaged 1/3 fewer pups than controls. Pups from these treated animals weighed less than controls and the weight differences persisted through weaning but were no longer significant at 56 days of age. Mice exposed to methylmercury in utero showed significant differences from controls in their behavior in a 2-way active avoidance shuttle box and in a punishment situation but not when tested in an open field, a water escape runaway or a conditioned suppression paradigm. Neither the mothers nor progeny of the mice exposed prenatally to methylmercury showed bahavioral deficits.     

An experimental model of pleural cancer. Value of orthotopic implantation of human tumor tissue in nude mice

In a comparison article we report that maternal PO exposure to 2.5 mg/kg all-trans retinoic acid (RA) daily for 3 consecutive days over gestational days (GD) 11-13 produces a 10% reduction in weight of cerebellum at 4 weeks of age, not accompanied by other malformations. Here we report the results of a preliminary behavioral analysis of offspring exposed gestationally to RA as above. Exposed dams were allowed to deliver normally, and litters were culled to eight pups (4 +/- 1 of each sex) at birth. Both male and female offspring were tested prior to weaning on GD 21. Thereafter females were killed on postnatal day (PND) 28 for verification of RA effects on regional brain weight, and all subsequent behavioral testing was conducted on males. Preweaning tests were restricted to negative geotaxis (PND 8-9) and open field activity (PND 22). Postweaning tests included open field activity (PND 43), auditory startle response (three times, on PNDs 22, 43, and 84), 2-week activity in residential running wheels (PNDs 62-76), complex maze performance for 5 consecutive days (PND 83-87), emergence latency (PND 106), and assessment of the behavioral response to an amphetamine challenge (PND 107). Males were then killed on PND 108 for verification of RA effects on regional brain weights. In this study, RA reduced weight of cerebellum but not striatum. Cerebellar weight was 92% of control values in PND 28 females, and this weight difference had diminished to 95% of control weight by PND 108 in males. There were no treatment effects on negative geotaxis, activity in a small open field, auditory startle amplitude, or latency to enter an illuminated alley from a dark chamber. Maze learning occurred at levels equal to or slightly better than controls. Running wheel activity was enhanced by RA exposure, whereas activity in response to an amphetamine challenge was reduced by such exposure. We conclude that RA doses low enough to produce mild weight reductions in cerebellum, without attendant malformations, can alter behavior. The precise nature of these alterations remains to be elucidated, but the findings reported here suggest that effects may be more pronounced on activity than on learning.     

Changes in dopamine, serotonin and their metabolites in discrete brain areas of rat offspring after in utero exposure to cocaine or related drugs

The concentrations of dopamine (DA), serotonin (5HT) and their metabolites were quantified in 5 brain areas of rats exposed to saline, cocaine (15 mg/kg b.i.d.), amitriptyline (10 mg/kg), or amfonelic acid (AFA, 1.5 mg/kg) throughout gestation. Male pups from 3 similarly treated dams were fostered to 2 surrogate dams. The process of breeding and rearing was repeated 4 times with new dams to build the groups to 4-12, since only one pup per litter was used for any one measurement. AFA was used to mimic the dopamine (DA) uptake blockade and stimulant properties of cocaine and amitriptyline was used to mimic the other pharmacological effects of cocaine. At postnatal days (PND) 30, 60, and 180, one pup per litter was removed for HPLC analysis of monoamines. A second pup received 0.3 mg/kg haloperidol, catalepsy assessed after 1 hr, and the brain used for analysis. The cataleptic response to haloperidol was unaffected by any prenatal treatment. The striatum from PND 30 cocaine rats had decreased levels of DA without a decrease in DA metabolites. At PND 60 in cocaine exposed rats, DA and DOPAC concentrations were increased, and 5HT levels were decreased in the striatum. The amitriptyline-exposed group exhibited decreased 5HT and 5-HIAA levels in the striatum. The hypothalamus of the cocaine group had lower levels of 5-HIAA, and other brain areas had a trend for lower levels of 5HT and 5-HIAA. At PND 180, DOPAC was increased in the striatum and prefrontal cortex of the cocaine group. Haloperidol-induced altered monoamine metabolism was unaffected by any prenatal treatment at any age. These data suggest that age-related changes in the DA and 5HT neurotransmission systems occur in rats exposed prenatally to cocaine. However, the ability of the dopaminergic system to respond to a challenge by a DA receptor blocker is unaltered by these in utero treatments.     

Oral methylphenidate improves spatial learning and memory in pre- and periadolescent rats.

Methylphenidate (MPD) is widely prescribed for attention-deficit/hyperactivity disorder in the United States. Patients, mostly school-age children, are taking the drug orally. To simulate the human condition, the authors used a cracker to administer methylphenidate orally (without the stress of handling) from Postnatal Day (PND) 22 to PND 40 and determined the effects of daily low-dose administration on the learning and performance of a radial arm maze win-shift task with all 8 arms baited. Number of entries to repeat, time to finish 8 entries, and days to reach criterion (at least 7 entries without errors for 4 out of 5 consecutive trials) were evaluated. An improvement during the first 7 days was revealed in both male and female rats treated with 3.0 mg/kg of oral methylphenidate compared with the controls. On PND 40, locomotor activity levels were not significantly different in the 3.0 mg/kg treated group compared with the controls during the initial 5 min or during the full 1 hr of recording. These data suggest that oral administration of low-dose MPD improves spatial learning and memory in both male and female preadolescent rats. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Mammalian artificial chromosomes as tools for gene therapy

Parkinson's disease (PD) is one of the most frequent disorders of the basal ganglia. From epidemiological studies there is a controversial discussion on the question whether tobacco smoking is correlated with a decreased incidence of PD. The present study aimed to elucidate the role of nicotine and its potential neuroprotective effects in a rodent model of PD. These effects may be related to an altered hydroxyl radical formation; this possibility was studied in vitro. Nicotine and alpha-phenyl-N-tert-butyl nitrone (PBN) were examined in a cell-free in vitro Fenton system (Fe3+/EDTA + H2O2) for their radical scavenging properties using the salicylate trapping method. Salicylic acid (0.5 mM) was incubated in the presence and absence of nicotine or PBN and the main products of the reaction of hydroxyl radicals with salicylic acid, namely 2,3- and 2,5-dihydroxybenzoic acid, were immediately determined using HPLC in combination with electrochemical detection. Nicotine and PBN were both able to significantly reduce hydroxyl radical levels at concentrations of 1, 2.5 and 5 mM. Interestingly, at 5 mM nicotine was able to reduce hydroxyl radical levels significantly more than the radical scavenger PBN (5 mM). To investigate the in vivo effects of nicotine, male C57BL/6 mice were used in the MPTP mouse model of PD. Nicotine (0.1 or 0.4 mg/kg s.c.) was administered twice daily for a period of 14 days. On day 8 a single injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 30 mg/kg s.c.) was given as well as an enhanced protocol of nicotine treatment (0.1 or 0.4 mg/kg s.c., 30 min before MPTP and 30, 90, 210, 330, 450, 570 min after MPTP) for a total of seven injections of nicotine. High dosage nicotine treatment significantly increased the MPTP-induced loss of body weight and resulted in a significantly decreased striatal dopamine content and an increased dopamine turnover in comparison with the MPTP-treated controls at day 15. However, the lower dosage of nicotine did not significantly alleviate the MPTP-induced effects, although some parameters showed a slight tendency in this direction. These results demonstrate that in vitro nicotine has radical scavenging properties which might suggest neuroprotective effects. In vivo experiments with nicotine, however, showed that a low dosage of nicotine did not alleviate the MPTP-induced dopamine depletion, but a large dosage even enhanced it.     

Hypothermic vocalizations of rat pups (Rattus norvegicus) and direct maternal search behavior.

Emissions of ultrasonic vocalizations (USVs) by rat pups (Rattus norvegicus) during hypothermia have consequences for recovery and warming. The effects on dam behavior of USVs emitted by 3- to 11-day-old pups during hypothermia at rectal temperatures between 18 and 22°C was investigated Rat dams were tested in a Y maze with the home cage as a start box. Dams were given, in one condition, a choice between a hypothermic pup emitting USVs or a hypothermic, silent (anesthetized) pup and, in the other, a choice between 2 hypothermic, silent pups. Although differing in some acoustic properties from normal isolation calls, USVs emitted by hypothermic pups both elicited maternal search behavior and acted as directional cues for dams, in comparisons with control dams exposed only to silent pups. Thus USVs of pups recovering from extreme hypothermia have communicative as well as physiological significance. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Medial prefrontal cortex lesions and spatial delayed alternation in the developing rat: Recovery of sparing?

In Exp 1, Long-Evans rat pups received medial prefrontal cortex (PFC) aspirations or sham surgery on Postnatal Day 10 (PND10) and were then trained on PND23 to perform 1 of 2 T-maze tasks: discrete-trials delayed alternation (DA) or simple position discrimination. Early PFC damage produced a selective failure to learn the DA task. In Exp 2, pups given the same lesion or sham surgery were trained on DA on PND19, PND27, or PND33. In relation to sham-operated controls, pups with PFC damage were impaired on PND19, somewhat impaired on PND27, and entirely unimpaired when tested on PND33. In Exp 3, pups given larger lesions of the frontal cortex on PND10 were impaired on DA when tested on PND23 but not when tested on PND33. These findings indicate that early PFC lesions result in a memory deficit around the time of weaning, which then recovers over the next 10–24 days of development. Moreover, the early deficit is selective for a late developing cognitive process (or processes) that is involved in acquisition of DA. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of 3,3'-iminodipropionitrile on acquisition and performance of spatial tasks in rats

3,3'-Iminodipropionitrile (IDPN) has been reported to disrupt learning and memory in rats (24). The present work addressed the effects of IDPN on tasks requiring the use of spatial information. Separate groups of male rats were dosed with IDPN (IP, in 1 ml/kg saline) for 3 consecutive days and tested in the following procedures: (a) step-through passive avoidance conditioning (0, 100, 150, and 200 mg/kg/day); (b) Morris water maze (MWM) acquisition and retention (0, 125, 150, 175, and 200 mg/kg/day); (c) radial arm maze (RAM) acquisition (0, 100, 200, and 400 mg/kg/day); (d) RAM steady-state performance (0, 200, and 400 mg/kg/day); (e) repeated acquisition in the RAM (0, and 200 mg/kg/day). The vestibular toxicity of IDPN resulted in alterations in spontaneous behavior or swimming deficits in 5 of 8 rats treated with 175 mg/kg/day and in all the animals dosed with 200 or 400 mg/kg/day. IDPN increased step-through PA latencies at 200 mg/kg/day but not at lower doses. In the MWM, no performance deficits were observed at the dose levels preserving the swimming ability of the animals. In both the acquisition and the steady-state RAM tasks, IDPN (400 mg/kg/day) induced an increase in both choice errors and perseverative errors. In the RAM repeated acquisition paradigm, IDPN (200 mg/kg/day) induced performance deficits that included a decreased rate of within-session reduction in errors. The present data show that IDPN disrupts performance of tasks requiring spatial learning and memory and indicate that these deficits can be in part caused by an acquisition deficit.     

Ventilation during simulated altitude, normobaric hypoxia and normoxic hypobaria

Maternal smoking increases the risk of the sudden infant death syndrome (SIDS) 2-4-fold. The mechanism is unknown but may be related to hypoxia responses. Recovery from hypoxic apnea by young mammals depends on gasping and bradycardia. We asked whether prenatal nicotine exposure, reported to reduce hypoxic survival in 2 day old rat pups, acted by impairing gasping or bradycardia. Pregnant rats were infused throughout gestation and 1 week postnatally with nicotine tartrate (NIC) 12 mg/kg per day or saline (CON). Maternal plasma nicotine was 134.4 +/- 42 ng/ml, significantly reducing pup body weight. Pups at 3-28 days were exposed to anoxia (97% N2/3% CO2) until gasping ceased, while breathing and heart rate were recorded. NIC and CON groups were not significantly different at any age, in baseline heart rate, respiratory rate, the time course for bradycardia, time to gasp onset, duration of gasping, or number of gasps, although most of these variables declined significantly with age. We conclude that responses to anoxia are not affected by prenatal high-dose nicotine.