Rats

Here we provide experimental evidence for the effects of prenatal nicotine exposure on measures of attention and impulsivity in adult male rats. Offspring of females exposed during pregnancy to 0.06 mg/ml nicotine solution as the only source of water (daily consumption: 69.6±1.4 ml/kg; nicotine blood level: 96.0±31.9 ng/ml) had lower birth weight and delayed sensorimotor development measured by negative geotaxis, righting reflex and grip strength. In the 5-choice serial reaction time test, adult rats showed increased numbers of anticipatory responses and omissions errors, more variable response times and lower accuracy with evidence of delayed learning of the task demands when the 1 s stimulus duration was introduced. In contrast, prenatal nicotine exposure had no effect on exploratory locomotion or delay-discounting test. Prenatal nicotine exposure increased expression of the D5 dopamine receptor gene in the striatum, but did not change expression of other dopamine-related genes (DRD4, DAT1, NR4A2, TH) in either the striatum or the prefrontal cortex. These data
suggest a direct effect of prenatal nicotine exposure on important aspects of attention, inhibitory control or learning later in life.

Animal models of prenatal nicotine exposure clearly indicate that nicotine is a neuroteratogen. Some of the persisting effects of prenatal nicotine exposure include low birth weight, behavioral changes and deficits in cognitive function, although few studies have looked for neurobehavioral and neurochemical effects that might persist throughout the lifespan. Pregnant rats were given continuous infusions of nicotine (0.96 mg/kg/day or 2.0 mg/kg/day, freebase) continuing through the third trimester equivalent, a period of rapid brain development. Because the third trimester equivalent occurs postnatally in the rat (roughly the first week of life) nicotine administration to neonate pups continued via maternal milk until postnatal day (P) 10. Exposure to nicotine during pre- and early postnatal development had an anxiogenic effect on adult rats (P75) in the elevated plus maze (EPM), and blocked extinction learning in a fear conditioning paradigm, suggesting that pre- and postnatal nicotine exposure affect anxiety-like behavior and cognitive function well into adulthood. In contrast, nicotine exposure had no effect on anxiety-like behaviors in the EPM in adolescent animals (P30). Analysis of mRNA for the α4, α7, and β2 subunits of nicotinic acetylcholine receptors revealed lower expression of these subunits in the adult hippocampus and medial prefrontal cortex following pre- and postnatal nicotine exposure, suggesting that nicotine altered the developmental trajectory of the brain.

The effects of repeated oral administration of Imidacloprid (IC) over 4 weeks on immune response, oxidative stress and hepatotoxicity were assessed. Forty-eight adult male albino rats were divided into two groups of twenty-four animals each. The control group was orally administered distilled water, while the IC-treated group was orally administered 1/100 LD50 (0.21 mg/ kg body weight) of IC insecticide daily. We found a significant increase in the total leukocyte count, total immunoglobulins (Igs) especially IgG. In contrast, significant decreases in phagocytic activity, chemokinesis and chemotaxis were observed in the IC-treated group compared to the control group. Histopathologically, the spleen tissues of the IC-treated rats displayed low numbers of lymphocytes, some of which appeared to be pyknotic. However, both fibroblasts and bundles, such as trabeculae, occurred in greater numbers. Similarly, thymus tissues in the IC-treated group showed lymphocytic depletion with pyknotic nuclei. Additionally, significant increases in the serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), alkaline phosphatase (ALP) and malondialdehyde (MDA) were observed in the IC-treated group. Accordingly, in the IC-treated group, heavily congested central vein and blood sinusoids were observed in the liver tissues; pyknotic nuclei were found throughout the hepatic tissue, and leukocyte infiltration was observed. In summary, these results suggest that exposure to 1/100 LD50 of IC induces immunotoxicity, oxidative stress, lipid peroxidation and hepatotoxicity.

L'imidaclopride (IMI) et l'acétamipride (ACE) appartiennent à la néonicotinoïdes, une nouvelle classe de pesticides, qui sont largement utilisés dans le monde pour protéger les cultures contre les insectes ravageurs et les animaux domestiques de puces. Ils agissent comme des agonistes des récepteurs nicotiniques de l'acétylcholine (nAChR) et leur toxicité sélective contre les insectes sont bien établis, tandis que leurs effets précis sur les nAChR mammifères restent à élucider. Des études antérieures ont rapporté que les néonicotinoïdes montrent des affinités faibles à l'ordre contre les différentes nAChR mammifère par dosage de liaison artificielle, ce qui est insuffisant pour la sécurité réelle. L'objectif de cette étude était de déterminer dans quelle mesure les néonicotinoïdes affecter le nAChR de rat neurones du cervelet, et de comparer leurs effets avec de la nicotine en utilisant in vitro excitateurs Ca afflux de dosage.

A subacute toxicity study of acetamiprid was undertaken in 72 female wistar rats in four groups (18 each). Three different concentrations of acetamiprid (25, 100 and 200 mg/kg of body weight) were administered orally to rats. Untreated rat served as control. The antibody titre of sheep red blood cells (SRBC) in all the treated groups and decrease in cell mediated immune response (CMI) were evaluated by delayed type hypersensitivity reaction to dinitroflurobenzene (DNFB). Our results revealed that in 200 mg/kg body treated rats, there were significant (Pd≤0.01) decrease in mean values of total leukocyte count and relative lymphocyte count in rats. Globulin was also decreased significantly (Pd≤0.01) in acetamiprid treated rats compared to control. There was a significant decrease (Pd≤0.01) in spleen weight in rats treated with 200 mg/kg dose as compared to control. Histopathological examination of spleen revealed depletion of lymphocytes from Malpighian corpuscles in all treated groups in a dose dependent manner. The results indicated that acetamiprid suppressed both CMI and antibody forming ability of lymphocytes.

Developmental neurotoxicity (DNT) studies are designed to investigate whether pre- or post-natal exposure to a toxicant affects neural development. Imidacloprid was administered in the diet to mated Sprague Dawley rats. The females were treated from gestation day 0 to 20 and then continued through the lactation day 21 at doses of 0, 100, 250 and 750 ppm, corresponding to an average daily intake of 0, 8, 19 and 54.7 mg/kg/day during gestation. The pups were indirectly exposed to imidacloprid for a total of 41 days (20 days in utero and 21 days via lactation). After weaning on postnatal day 21 pups were given untreated feed.

Brain tissue from 10 pups/sex/group were analyzed on postnatal days 11 and 75. On post-natal day 11, female pups from the 750 ppm group had a decreased caudate putamen width and a substantial reduction in the thickness of the corpus callosum. Morphometric brain measurements were not performed in the intermediate and low dose groups.

Thiamethoxam is a neonicotinoid insecticide, a group of pesticides that acts selectively on insect nicotinic acetylcholine receptors (nAChRs), with only a little action on mammalian nAChRs. Nevertheless, the selectivity of neonicotinoids for the insect nAChRs may change when these substances are metabolized. Therefore, we aimed to determine the potential effects of thiamethoxam on mammalian brain, testing the performance in the open field and elevated plus-maze of rats exposed to this insecticide and, in order to establish the neurochemical endpoints, we measured the acetylcholinesterase activity in different brain regions (hippocampus, striatum and cortex) and the high-affinity choline uptake (HACU) in synaptosomes from rat hippocampus.

Treated animals received thiamethoxam (25, 50 or 100 mg/kg) for 7 consecutive days. The results showed that treatment with thiamethoxam induced an increase in the anxiety behavior at two doses (50 or 100 mg/kg). Moreover, there was a significant decrease in both HACU and acetylcholinesterase activity. Our hypothesis is that thiamethoxam (or its metabolites) could be acting on the central rats nAChRs. This would produce an alteration on the cholinergic transmission, modulating the anxiety behavior, acetylcholinesterase levels and HACU.