Forced swimming stress increases natatory activity of lead-exposed mice.

Recent evidence points to the relationship between lead toxicity and the function of the hypothalamic-pituitary-adrenal axis, which suggests that lead exposure could influence how an individual cope with stress. Here we test this hypothesis by investigating the behavioral effects of lead exposure in mice during the forced swimming test (FST), a parading in which animals are exposed to a stressful situation and environment. Swiss mice received either 180 ppm or 540 ppm of lead acetate (Pb) in their ad-lib water supply for 60-90 days, starting at postnatal day 30. Control (Ctrl) mice drank tap water. At the end of the exposure period, mice were submitted to a 5-min session of FST or to an open-field session of the same duration. Data from naïve animals showed that corticosterone levels were higher for animals tested in the FST compared to animals tested in the open-field. Blood-lead levels (BLL) in Pb-exposed mice ranged from 14.3 to 106.9 µg/dL. No differences were observed in spontaneous locomotion between Ctrl and Pb-exposed groups in the open-field. However, in the FST, Pb-treated mice displayed higher swimming activity than Ctrl ones and this effect was observed even for animals with BLL higher than 20 µg/dL. Furthermore, significant differences in brain glutathione levels, used as an indicator of led toxicity, were only observed for BLL higher than 40 µg/dL. Overall, these findings suggest that swimming activity in the FST is a good indicator of lead toxicity and confirm our prediction that lead toxicity influences behavioral responses associated to stress.

Hyperactivity and memory/learning deficits evoked by developmental exposure to nicotine and/or ethanol are mitigated by cAMP and cGMP signaling cascades activation.

Pregnant smoking women are frequently episodic drinkers. Here, we investigated whether ethanol exposure restricted to the brain growth spurt period when combined with chronic developmental exposure to nicotine aggravates memory/learning deficits and hyperactivity, and associated cAMP and cGMP signaling disruption. To further investigate the role of these signaling cascades, we verified whether vinpocetine (a phosphodiesterase inhibitor) ameliorates the neurochemical and behavioral outcomes. Swiss mice had free access to nicotine (NIC, 50 µg/ml) or water to drink during gestation and until the 8th postnatal day (PN8). Ethanol (ETOH, 5 g/kg, i.p.) or saline were injected in the pups every other day from PN2 to PN8. At PN30, animals either received vinpocetine (20 mg/kg, i.p.) or vehicle before being tested in the step-down passive avoidance or open field. Memory/learning was impaired in NIC, ETOH and NIC + ETOH mice, and vinpocetine mitigated ETOH- and NIC + ETOH-induced deficits. Locomotor hyperactivity identified in ETOH and NIC + ETOH mice was ameliorated by vinpocetine. While cyclic nucleotides levels in cerebral cortex and hippocampus were reduced by NIC, ETOH and NIC + ETOH, this outcome was more consistent in the latter group. As observed for behavior, vinpocetine normalized NIC + ETOH nucleotides levels. pCREB levels were also increased in response to vinpocetine, with stronger effects in the NIC + ETOH group. Exposure to both drugs of abuse worsens behavioral and neurochemical disruption. These findings and the amelioration of deleterious effects by vinpocetine support the idea that cAMP and cGMP signaling contribute to nicotine- and ethanol-induced hyperactivity and memory/learning deficits.

Maternal protein-free diet during lactation programs male Wistar rat offspring for increased novelty-seeking, locomotor activity, and visuospatial performance.

It is well established that chronic undernutrition has detrimental impacts on brain development and maturation. However, protein malnutrition during the period specifically encompassing the brain growth spurt has not been widely studied, particularly regarding its effects on adolescent and adult offspring behavior. Here, we assessed the effects of a protein-free diet during the 1st 10 postnatal days on the macronutrient content of the milk produced by lactating Wistar rats, on their maternal behavior, and on the offspring's behavior. Lactating dams were fed either a protein-free or a normoprotein diet from litter parturition to Postnatal Day 10 (P10). All dams received the normoprotein diet after P10. Offspring were tested in the elevated plus-maze (anxiety-like behavior), hole board arena (novelty-seeking and locomotor activity), and radial arm water maze (memory-learning) at either P40 (adolescents) or P90 (adults). The protein-free diet reduced milk protein content at P10 but not at P20. Carbohydrate and lipid contents were unaffected. Serum corticosterone levels in the offspring (at P10, P40, or P90) and dams (at P21) were not affected by the protein-free diet. Maternal behavior was also unchanged. In the offspring, no differences were observed between groups regarding anxiety-like behaviors at both ages. The protein-free diet increased adolescent locomotor activity as well as adult novelty-seeking behavior and memory performance. Our results indicate that the brain growth spurt period is particularly sensitive to protein malnutrition, showing that even a brief nutritional insult during this period can cause specific age-dependent behavioral effects on the offspring. (PsycINFO Database Record