Neurobehavioral changes produced in rats by prenatal exposure to carbon monoxide.

Wistar 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 impairment.

Up-regulation of polysialic acid in peripheral myelinated axons of rat chronically exposed to 2,5-hexanedione.

Myelinated nerve fibres isolated from Wistar rats chronically exposed to 2,5-hexanedione (0.8 ml/kg/day, intraperitoneally) over a period of 20 days, were stained with lectin-horseradish peroxidase conjugates. The lectins with high affinity for terminal D-galactopyranosyl residues, Bandeiraea simplicifolia-B4 (BSA I-B4) and peanut agglutinin (PNA), showed glycoconjugates in the control nodes of Ranvier. In the treated animals, application of PNA-HRP caused weak reactivity to the node of Ranvier; digestion with sialidase prior to the application of PNA-HRP conjugate enhanced reactivity, thus revealing the presence of a sialoglycoprotein. The results indicate that glycoconjugates of the Ranvier node undergo a rearrangement during exposure to 2,5-hexanedione. In particular, neutral glycoproteins with terminal galactose are replaced by sialoglycoproteins. These findings are consistent with the proposed role of polysialic acid as a regulator of axonal behaviour during regeneration.

Effects of chronic ethanol intake at a low dose on the rat brain dopaminergic system.

The effects of 8-week ethanol treatment (3% v/v in drinking water) on the rat brain dopaminergic system were investigated. Chronic ethanol consumption induced a significant increase in the number of dopamine D1 receptor sites in the caudate putamen. Conversely, no significant changes were observed in D2 receptor density or affinity. Biochemical results were in agreement with behavioral data, as amphetamine-induced locomotor hyperactivity was significantly higher in ethanol-treated rats in comparison to controls. Moreover, grooming behavior in response to SKF 38393, a selective agonist of D1 receptors was potentiated in ethanol-treated rats, whereas locomotor hyperactivity induced by LY 171555 (a selective agonist of D2 receptors) was not affected by ethanol treatment. The results indicate that changes in dopamine receptors may occur in the central nervous system at levels of ethanol intake that do not induce tolerance or dependence.

Behavioral changes produced in rats by developmental exposure to flumazenil, a benzodiazepine receptor antagonist.

1. 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.

Developmental aspects of neurobehavioural toxicity.

Previous work on the developmental aspects of neurobehavioural toxicity in rats and mice has shown the reliability of a variety of procedures aimed at assessing changes that may have widespread functional consequences, for example: (i) modified Fox batteries to study the maturation of various reflexes and responses after birth, (ii) activity/habituation and analgesia tests with age-specific profiles of reactivity to selected drug challenges, and (iii) simple learning tasks such as active and passive avoidance [1]. We will now summarize more recent work on other portions of the behavioural repertoire which deserve to be thoroughly assessed in "higher-tier" studies.

A new experimental approach for detecting emotional and motivational changes produced by neuroactive compounds in rodents.

A new potential approach for detecting subtle changes of emotional and motivational states in rodents is represented by the analysis of ultrasonic vocalizations emitted in a variety of situations. The ultrasonic calls differ somewhat in their physical characteristics depending on the species and on the situation. The results of our studies on the effects of various neuroactive substances on ultrasonic emissions during neonatal life and during sexual behaviour are briefly described here together with what is known of the biological function of the calls.

Neurobehavioral changes produced by developmental exposure to benzodiazepines.

The results reported in this review show that prenatal and/or postnatal administration of benzodiazepines, at dose levels below those associated with overt signs of neurotoxicity, produces both short- and long-term alterations in rats. Most of these behavioral changes are characterized by altered activity patterns and emotional/motivational responsiveness to environmental challenges.