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Appropriate endpoints for the characterization of behavioral changes in developmental toxicology
No full textThe present paper is devoted to second- and higher-tier test methods for the characterization of behavioral changes produced in rodents by exposure to noxious agents during development. The paper analyzes a series of end points that are informative about specific processes and underlying regulatory mechanisms but require greater technical sophistication and larger investments than first-tier end points. This applies to ultrasonic emissions in successive postnatal periods; to mother-pup interactions, including appropriate cross-fostering controls, to social (including sexual) interaction tests from the infantile to the young adult stage; and to a variety of conditioning and learning tests using both positive and negative reinforcemen
NEUROBEHAVIORAL CHANGES PRODUCED IN RATS BY PRENATAL EXPOSURE TO CARBON MONOXIDE
No full textWistar female rats were exposed to relatively mild concentrations of carbon monoxide (75 and 150 ppm) from day 0 to day 20 of pregnancy. The results show that prenatal exposure to CO (150 ppm) produced a significant reduction in the minimum frequency of ultrasonic calls emitted by rat pups removed from their nest. Moreover, a significant decrease in the responsiveness (rate of calling) to a challenge dose of diazepam (0.25 mg/kg) was found in male pups exposed to CO (150 ppm) during gestation. Prenatal CO (75 and 150 ppm) did not significantly affect locomotor activity or D-amphetamine-induced hyperactivity in both 14- and 21-day-old animals. Furthermore, adult male rats exposed to this chemical (150 ppm) during gestation exhibited significant alterations in the acquisition of an active avoidance task. CO-induced learning disruption does not seem to be linked to changes in the emotionality of animals. These findings suggest that gestational exposure to CO induces in rat offspring both short- and long-term behavioral changes characterized by altered ontogeny of emotional responsiveness to environmental challenges and by learning impairmen
Changes in peripheral nervous system activity produced in rats by prenatal exposure to carbon monoxide
No full textThe present experiments were designed to investigate whether alterations of peripheral nervous system activity may be produced in male Wistar rats by prenatal exposure (from day 0 to day 20 of pregnancy) to relatively low levels of CO (75 and 150 ppm). The voltage clamp analysis of ionic currents recorded from sciatic nerve fibres showed that prenatal exposure to CO produced modifications of sodium current properties. In particular, in 40-day-old rats exposed to CO (75 and 150 ppm) during gestation, the inactivation kinetics of transient sodium current were significantly slowed. Analysis of the potential dependence of steady-state Na inactivation, h(infinity) (V), showed that the percentage of the maximum number of activatable Na channels at the normal resting potential (-80 mV) was increased to almost-equal-to 85% in CO-exposed rats. Moreover, the voltage-current relationship showed a negative shift of sodium equilibrium potential in CO treated animals. In 270-day-old CO-exposed rats, parameters of sodium inactivation were not significantly modified; the reversal potential was still lower with respect to controls. The results indicate that prenatal exposure to mild CO concentrations produces reversible changes in sodium inactivation kinetics and on irreversible change in sodium equilibrium potential. These alterations could reflect CO influence on the rate of ion channel developmen
Irreversible impairment of active avoidance behavior in rats prenatally exposed to mild concentration of carbon monoxide
No full textWistar female rats were exposed to relatively mild concentrations of carbon monoxide (75 and 150 ppm) from day 0 to day 20 of pregnancy. The results show that prenatal exposure to CO (150 ppm) significantly impairs the acquisition of a two-way active avoidance task in 3-month-old male rats as well as the acquisition and reacquisition of this schedule in 18-month-old animals subjected to six daily 20-trial sessions. These deficits do not seem to be attributable to alterations of a non-associative nature, as the intertrial activity and the escape response latencies in CO exposed animals were not significantly affected with respect to controls. These findings, showing that gestational exposure to CO induces in rat offspring permanent learning and memory impairment, confirm that the offspring of smoking mothers may be at considerably greater risk than current epidemiological studies on birthweight and neonatal mortality suggest
Behavioral changes produced in rats by developmental exposure to flumazenil, a benzodiazepine receptor antagonist
No full text1. Prolonged administration of a benzodiazepine receptor antagonist, such as flumazenil (given to the mother at a dose of 3 mg/kg s.c. from day 14 to day 20 of gestation), produced subtle behavioral changes in rat pups.
2. Flumazenil treatment decreased the rate of ultrasonic vocalization in 15-day old male pups removed from their nest.
3. No significant changes in the locomotor activity of the flumazenil-treated group with respect to controls was found at the end of the second and fourth postnatal week.
4. These results suggest that late prenatal exposure to flumazenil induces in rat offspring behavioral changes characterized by decreased emotional responsiveness to environmental challenges
Immunological changes produced in rats by prenatal exposure to carbon monoxide
No full textWistar female rats were exposed to relatively mild concentrations of carbon monoxide (CO) (75 and 150 p.p.m.) from day 0 to day 20 of pregnancy. The results show that splenic macrophage phagocytosis of Candida albicans was significantly decreased in 15 and 21 day old male rats exposed to CO (150 p.p.m.) during pregnancy. Moreover, splenic macrophage killing was significantly reduced in 15 day old male pups prenatally exposed to 75 and 150 ppm of CO. Prenatal CO (150 p.p.m.) significantly decreased splenic macrophage O-2(-) release in both 15 and 21 day old pups. CO-induced alterations in the immune system were not observed in 60 day old rats. These findings indicate that gestational exposure to relatively mild concentrations of CO induces in rat offspring reversible immunological changes characterized by an altered splenic macrophage functio
Lectin binding pattern of Schwann cells and macrophages in 2,5-hexanedione-induced axonal degeneration in rats
No full textThe lectin binding pattern of both Schwann cells and macrophages has been studied during axonal degeneration induced in the rat sciatic nerve by chronic administration of 2,5-hexanedione (0.8 ml/kg per day i.p. for 20 days). In particular, the present study aimed to establish a possible relationship between macrophage activation and expression of lectin binding sites. To identify and distinguish between Schwann cells and macrophages, electron microscopy was combined with the lectin staining method. On 2,5-hexanedione injury, a drastic disorganization of both axon and myelin sheath occurred and nerve fibers were replaced by a chain of ovoids. Besides the well-established concept that Schwann cells and macrophages cooperate in the removal of the myelin debris during axonal degeneration, evidence is presented that expression of binding sites to lectins is closely related to macrophage activation. Monocytes occasionally present in control nerves were labelled only by Con A and sialidase-peanut sequence; in 2,5-hexanedione degeneration monocytes, prephagocytes (macrophages with minute bubbles) and phagocytes (macrophages with large bubbles) were labelled also by peanut, wheat germ and BSA I-B-4; moreover, phagocytes were labelled by soybean as well, thus showing a clearly differentiation-dependent binding pattern. Since changes in lectin binding pattern may reflect changes in complex carbohydrate structures, the results show that the expression of certain glycoproteins may be closely related to activation of macrophages in response to toxic injuries
Alteration in the ontogeny of rat pup ultrasonic vocalization produced by prenatal exposure to nitrogen dioxide
No full textWistar female rats were exposed to low concentrations of nitrogen dioxide, NO2 (1.5 and 3 ppm) from day O to day 20 of pregnancy. The results show that prenatal exposure to this oxidant gas produced significant changes in the duration pattern of ultrasonic vocalizations emitted by male pups removed from their nest. In particular, a significant decrease in the length of ultrasonic calls was found in both 10- and 15-day-old rats exposed to N0(2) (3 ppm) during gestation. These alterations were found at dose levels which did not significantly affect reproduction parameters, body weight gain and motor activity development. These findings suggest that gestational exposure to NO2, at concentrations below those associated with overt signs of toxicity, induces in rat offspring subtle behavioral changes characterized by altered ontogeny of ultrasonic emission
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