+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Critical analysis of potential body temperature confounders on neurochemical endpoints caused by direct dosing and maternal separation in neonatal mice: a study of bioallethrin and deltamethrin interactions with temperature on brain muscarinic receptors



Critical analysis of potential body temperature confounders on neurochemical endpoints caused by direct dosing and maternal separation in neonatal mice: a study of bioallethrin and deltamethrin interactions with temperature on brain muscarinic receptors



Journal of Applied Toxicology 23(1): 9-18



The present investigation was conducted to understand better possible confounding factors caused by direct dosing of neonatal mice during the pre-weaning developmental period. By direct dosing, pups might encounter thermal challenges when temporarily removed from their 'natural habitat'. Typically, this leads to a cold environment and food deprivation (impaired lactation) and modulation of the toxic potency of the substance administered. Growth retardation as a consequence of such behavioural changes in pups makes it increasingly difficult to differentiate specific from non-specific mechanisms. Neonatal NMRI mice were dosed daily by gavage (0.7 mg kg(-1) body wt.) from postnatal day (PND) 10-16 with S-bioallethrin, deltamethrin or the vehicle. Then the pups, including their non-treated foster dams, were subjected temporarily for 6 h day to a hypo-, normo- or hyperthermic environment, which was followed by normal housing. The measured temperatures in the environmental chambers were ca. 21, 25 and 30 degrees C, respectively. Thus, temperatures in the hypo- and normothermic groups are comparable to the temperatures commonly present in testing laboratories, whereas the hyperthermic condition is that temperature typically present in the 'natural habitat' of pups. A deviation from the normal behaviour of both pups and dams was observed in the hypo- and normothermic groups. In these groups the rectal temperatures of pups were markedly decreased, especially in the early phase of the study (PND 10-12). Neonates that received either test substance displayed changes in body weights and brain weights at terminal sacrifice (PND 17) when subjected temporarily to a non-physiological environment. An enormous influence of environmental temperature on the density of muscarinic receptors in the crude synaptosomal fraction of the cerebral cortex was ascertained. In summary, these results demonstrate that the direct dosing of thermolabile neonatal mice by gavage is subject to significant artefacts that render the interpretation of findings from such studies difficult. It appears that if direct dosing of neonatal pups is mandated, and inhalation is a relevant route of exposure, the combined inhalation exposure of dams with their litters is an alternative procedure that does not cause disruption of the 'natural habitat' of pups. However, owing to their higher ventilation, under such conditions the pups may receive dosages at least double those of the dams.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 010396252

Download citation: RISBibTeXText

PMID: 12518331

DOI: 10.1002/jat.873


Related references

Effects of two pyrethroids, bioallethrin and deltamethrin, on subpopulations of muscarinic and nicotinic receptors in the neonatal mouse brain. Toxicology and Applied Pharmacology 102(3): 456-463, 1990

Neonatal exposure to a type-I pyrethroid (bioallethrin) induces dose-response changes in brain muscarinic receptors and behaviour in neonatal and adult mice. Brain Research 645(1-2): 318-324, 1994

The significance of low body temperature for induction of chemical temperature regulation. II. Cold tremor caused by decrease of low body temperature in constant, increased skin and brain temperature. Pflugers Archiv für die Gesamte Physiologie des Menschen und der Tiere 274: 115-124, 1961

Neurotoxic effects of two different pyrethroids, bioallethrin and deltamethrin, on immature and adult mice: changes in behavioral and muscarinic receptor variables. Toxicology and Applied Pharmacology 108(1): 78-85, 1991

The significance of low body temperature for the induction of chemical temperature regulation. I. Cold tremor caused by decrease of low body temperature in constant, increased skin temperature. Pflugers Archiv für die Gesamte Physiologie des Menschen und der Tiere 274: 97-114, 1961

Relationship between trh induced changes in body temperature and brain trh receptors in five strains of mice. Federation Proceedings 45(3): 406, 1986

Direct measurement of brain temperature during and after intraischemic hypothermia: correlation with behavioral, physiological, and histological endpoints. Journal of Neuroscience 14(12): 7726-7734, 1994

The effect of acclimation temperature and removal of peripheral temperature receptors on body temperature preference in the cockroach, Periplaneta americana. Journal of Thermal Biology 114: 209-212, 1986

The effect of acclimation temperature and the removal of peripheral temperature receptors on body temperature preference in the cockroach periplaneta americana. Journal of Thermal Biology 11(4): 209-212, 1986

Neurochemical study of TA-0910, a new TRH analog effects of chronic treatment on TRH, muscarinic acetylcholine and D-2 dopamine receptors in rat brain. Japanese Journal of Pharmacology 61(Suppl. 1): 249P, 1993

Noradrenergic afferents and receptors in the medial preoptic area: neuroanatomical and neurochemical links between the regulation of sleep and body temperature. Neurochemistry International 50(6): 783-790, 2007

The Significance of Internal Body Temperature for the Chemical Temperature Regulation in Dogs in Light Anesthesia. Ii. Isolated Lowering of Brain Temperature. Pflugers Archiv für die Gesamte Physiologie des Menschen und der Tiere 278: 350-360, 1963

Direct effects of climate on cattle. 1. Some observations on the skin temperature, body temperature, respiration rate and pulse rate of dairy stock under normal temperature conditions. N.Z. J. Sci. Technol. [A, 1954

Measurement of body temperature in neonatal mice. Journal of Applied Physiology: Respiratory Environmental and Exercise Physiology 43(6): 1102-1105, 1977