PubMed Health⌕ Search

Biomedical subjects

C F Mactutus

Publications and source records attributed to C F Mactutus.

At least 37 records · Page 2Linked to original sources
PubMed1985

Moderate prenatal carbon monoxide exposure produces persistent, and apparently permanent, memory deficits in rats.

The effects of moderate (150 +/- 2 ppm) prenatal carbon monoxide (CO) exposure (maternal HbCO concentrations of 15.6 +/- 1.1%) on learning and memory were assessed in young and aged adult rats using a two-way active avoidance paradigm. In experiment 1, the prenatal CO-exposed rats at 120 days of age acquired a conditioned avoidance response equally well as control animals in a 100-trial session. However, following a 24-hr interval the CO-exposed rats failed to demonstrate significant retention of the task as indicated by the absence of significant improvement in performance over the indicated by the absence of significant improvement in performance over the previous day; control subjects did show significant retention. In experiment 2, in which 120-day-old animals received 50 training trials per day until a criterion of ten consecutive avoidance responses was met, the prenatal CO-exposed subjects again acquired the task as well as control animals. When tested for retention 28 days later, a significant memory impairment was again observed in terms of trials required to reattain the avoidance criterion as well as in total percent avoidance responding. In neither experiment did an analysis of initial or average latency to escape the footshock stimulus reveal any significant alterations. These latter results suggest that the observed performance impairment reflected a memory deficit and not a disruption of sensory, motor, or motivational factors. In experiment 3, prenatal CO-exposed rats approximately 1 year of age (300-360 days of age) showed impairment relative to air-exposed controls in both the original learning and retention of the two-way avoidance response. Again, however, there was no evidence for alterations in performance factors per se. Collectively these data indicate that while young adult rats prenatally exposed to 150 ppm CO demonstrate an associative deficit restricted to memory impairment, aged adults similarly exposed during the prenatal period display a more pronounced deficit similar to that recently reported for animals tested as juveniles. The importance of parametric manipulations in uncovering long-term toxicity is also discussed.

Aging↗
PubMed1985

Evaluation of long-term consequences in behavioral and/or neural function following neonatal chlordecone exposure.

The effects of neonatal exposure of rats to chlordecone, during the major postnatal period of neuroendocrine differentiation were assessed after the animals matured to 90 days of age. On day 4 postpartum, pups received a s.c. injection of either DMSO vehicle or chlordecone (1 mg/pup) dissolved in DMSO. The neonatal exposure produced a significant sex-dependent alteration in adult body weight; chlordecone-exposed males were lighter than vehicle-exposed controls and chlordecone-exposed females were heavier than vehicle-exposed controls. Behavioral tests sensitive to neonatal chlordecone exposure during preweaning development--i.e., spectral analysis of movement, activity, and auditory startle responsiveness--gave no statistically significant evidence for residual effects of the early organochlorine treatment. When challenged with harmine, a known tremorogen with putative effects on olivocerebellar pathways, chlordecone-exposed males were less responsive than vehicle-exposed littermates in a spectral analysis of movement. The movement spectrum of chlordecone-exposed females was not differentially sensitive to the harmine challenge. However, subsequent evaluation of the auditory startle reflex indicated that harmine interacted with the neonatal treatment and sex of the animal; chlordecone-exposed males were less responsive and chlordecone-exposed females more responsive than same sex vehicle-exposed littermates. The responsiveness to a d-amphetamine challenge, expressed as a ratio of baseline activity in a pre- and post-test design, suggested the chlordecone-exposed males gave an exaggerated response to the drug challenge. Collectively, these findings suggest that the neonatal chlordecone exposure had a significant organizational effect on the development of behavioral and/or neural function. These findings also suggest the predictive utility of early behavioral tests; that is, long-term alterations were noted in each component of the toxicological syndrome previously identified during preweaning development.

Animals↗
PubMed1985

Experimental design considerations: a determinant of acute neonatal toxicity.

Few studies have investigated the potential developmental differences resulting from treating neonatal rat pups in either split-litter or whole-litter (nested) experimental designs. We directly compared rat pups dosed with triethyl lead (TEL) via both split-litter (representing all dosage groups within a single litter) and nested (all pups randomly assigned to a single litter receive the same dose) designs. The nested design was chosen to produce a uniform behavioral pattern across pups within each litter, whereas the split-litter design was chosen to promote pup competition and differential maternal care. On postpartum day 5, pups were administered either 12, 13, 14, or 15 mg/kg TEL, with each design represented by 12 litters. Although the LD50 values for the two designs were not significantly different, there were significantly more deaths in the 12 mg/kg dosage group within the split-litter design than in the nested design group. Preweaning survival times for split-litter dosed animals were also decreased. In addition, significant growth reduction (7-16%) was observed in the split-litter group, relative to the nested design animals during the preweaning period. These results suggest that neonatal toxicity is not independent from experimental design considerations, and that the factors of littermate competition and/or pup-induced maternal care deserve further study.

Animals↗
PubMed1985

Effects of 5,5-diphenylhydantoin (phenytoin) on neurobehavioral toxicity of organochlorine insecticides and permethrin.

Rats were given various doses of chlordecone, 1,1,1-trichloro-2,2-bis(p-chloro-phenyl)ethane (DDT) and lindane and tested for neurobehavioral toxicity up to 24 hr postdosing. The organochlorines either had no effect or increased responsiveness to an acoustic stimulus at subconvulsant doses. Only chlordecone and p,p'-DDT produced tremor. For purposes of comparison, the neurobehavioral effects of permethrin were also studied; this pyrethroid insecticide produced tremor and hyperresponsiveness similar to that of p,p'-DDT. Pretreatment with phenytoin significantly reduced the tremor and hyperresponsiveness produced by p,p'-DDT and permethrin. On the other hand, pretreatment with phenytoin increased the responsiveness of animals dosed with chlordecone or lindane, suggesting that these agents differ in their mechanism of action from p,p'-DDT and permethrin. The results of our experiments also indicate that care should be taken in the choice of agents, particularly anticonvulsants, to be used to treat symptoms of insecticide toxicity.

Animals↗
PubMed1984

Prenatal exposure to carbon monoxide: learning and memory deficits.

Exposing pregnant rats to carbon monoxide (150 parts per million) produced only minor reductions in the birth weights of the pups and gave no evidence of overt teratogenesis. However, behavioral evaluation of learning and memory processes in a two-way avoidance task suggested a functional deficit in the central nervous system of the exposed offspring. Multiple dependent measures and specific control groups confirmed that this deficit was independent of nonassociative or motivational alterations.

Animals↗
PubMed1982

Nonmonotonic age changes in susceptibility to hypothermia-induced retrograde amnesia in rats.

The effects of post-training and/or pretesting body cooling on retention of Pavlovian discriminated fear conditioning were examined in preweanling (16-day) and weanling (23-day) rats. Twenty-four retention was assessed in 16- and 23-day-old rats receiving hypothermia after training, after training and prior to testing, or at neither time. Amnesia was present in the preweanling but not weanling rats. Recovery from amnesia was not observed in the preweanling rats followed a second cooling treatment. Control groups indicated the differential amnesia was not the result of differences in 24 hr baseline retention, depth of hypothermia cooling, rate of recovery from hypothermia treatment, or body temperature immediately post-testing. The results are discussed with respect to current views of infantile amnesia and the growing evidence for similar nonmonotonic functions during ontogeny.

Age Factors↗
PubMed1982

Chlordecone neurotoxicity: a brief overview.

Chlordecone or Kepone is a polycyclic chlorinated hydrocarbon insecticide that produces hyperexcitability, tremor, and other signs of nervous system toxicity. In addition, chlordecone has estrogenic-like effects and disturbs neuroendocrine function. Studies at the neurochemical level indicate that chlordecone inhibits neurotransmitter uptake; steady-state levels of biogenic amines are generally resistant to chlordecone, especially in mice. At the subcellular level, chlordecone may destabilize membrane function by altering energy metabolism and/or the disposition of ions required for neural transmission.

Animals↗
PubMedDate not supplied

Workshop on the qualitative and quantitative comparability of human and animal developmental neurotoxicity, Work Group II report: testing methods in developmental neurotoxicity for use in human risk assessment.

The Work Group addressed the design and content of a basic screening battery for detecting or flagging developmental neurotoxicity. It was agreed that a basic screening battery should be incorporated routinely into any developmental or reproductive toxicity study conducted for risk assessment purposes, and that a "triggered" stand-alone developmental neurotoxicity study, as exemplified by the current EPA proposal, should include greater in-depth evaluation of CNS function and pathology. Time constraints did not permit the group to address the design or content of such a stand-alone study. It was acknowledged unanimously that a basic screening battery may provide more information than simply the detection of neurotoxicity; however, it should not be expected to provide detailed dose-response information nor to identify the precise mechanism of agent action. The Work Group also agreed that a basic screening battery should include evaluation of multiple CNS functions, that observed alterations may be indicative of primary or secondary effects on the nervous system, that the test methods selected may differ based on what is known about the agent, and that the protocol for study conduct can be as important as the methods employed. In light of these assumptions, the Work Group recommended schedules for monitoring offspring development using measures of: 1) physical landmarks, 2) brain weights, 3) neuropathology, 4) functional observations, 5) motor activity, 6) reactivity, and 7) learning and memory. The species tested, sample sizes, treatment parameters, etc., would be determined by the type of developmental or reproductive toxicity study into which the basic screening battery was incorporated.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗