Dorota Wiaderna

Behavioral Changes Following 4-Week Inhalation Exposure to Pseudocumene (1,2,4-Trimethylbenzene) in the Rat

Pseudocumene (1,2,4-trimethylbenzene, TMB) is a component of several solvent mixtures. During recent studies on rats we investigated the effect of a 4-week (6 h/day, 5 days/week) inhalation exposure to TMB at concentrations of 0, 25, 100, or 250 ppm on radial maze performance, open field activity, passive avoidance, active two-way avoidance, and shock-induced changes in the pain sensitivity reflecting the magnitude of the shock-induced fear response (hot plate test). The tests were performed between days 14 and 54 after the last exposure. The radial maze performance was not disturbed in any dose group. During testing in the open field grooming was significantly increased in rats exposed to 100 ppm TMB. In rats exposed to 100 and 250 ppm TNB, a foot shock applied after stepping off an elevated platform (a safe area) resulted in a significantly smaller increase in the step-down latency (i.e., passive avoidance, on days 3 and 7 after the foot shock) than in sham-exposed animals. Learning of a two-way active avoidance was slightly retarded in rats exposed to 250 ppm of TMB. Results of the hot plate test revealed no differences between groups in the paw sensitivity to heat (54.5 degrees C) before a 2-min intermittent food shock, but in rats exposed to 100 and 250 ppm of TMB the foot shock-induced fear response persisted apparently longer. These results suggest that inhalation exposure to TMB may lead to long-lasting disturbances in CNS functions.

Behavioral Effects Following Subacute Inhalation Exposure to m-Xylene or Trimethylbenzene in the Rat: A Comparative Study

Trimethylbenzene (TMB), like xylene (dimethylbenzene), is a significant constituent of some industrial solvent mixtures. In earlier studies, we found that in the rat a subacute low-level inhalation exposure to some of the TMB isomers may result in behavioral alterations detectable weeks after the exposure [Neurotoxicol Teratol 19;1997:327; Int J Occup Med Environ Health 11;1998:319]. The purpose of the present study was to compare m-xylene (XYL) and each of the TMB isomers: 1,2,3-TMB (hemimellitene - HM), 1,2,4-TMB (pseudocumene - PS), and 1,3,5-TMB (mesitylene - MES) with respect to the ability for inducing behavioral effects in the rat. The rats (10-11 animals per group) were exposed repeatedly for 4 weeks (6 h per day, 5 days per week) to XYL (XYL group), HM (HM group), PS (PS group) or MES (MES group) at 100 ppm, or sham exposed (C group) in 1.3 cu/m dynamic inhalation chambers. Starting 2 weeks after exposure the following forms of rats behavior were assessed: radial maze performance, spontaneous activity in an open field, learning and retention of passive and active (two-way) avoidance response, and heat-induced paw licking before and after a 2 min footshock (a test for assessment of the stress response). None of the solvent-exposed groups differed considerably from the control one with respect to the radial maze performance. Compared to control rats, the rats of the XYL, PS and MES groups, but not those of HM group, showed a significantly higher spontaneous locomotor activity in the open field, an impaired passive avoidance learning and significantly longer paw-lick latencies 24 h after footshock. Acquisition, but not retention, of the two-way active avoidance response was significantly impaired in all solvent-exposed groups. The XYL group did not differ significantly from PS, MES or HM group in any of the behavioral parameters. The above results show that a short-term exposure to any of the TMB isomers or m-xylene at concentration as low as 100 ppm may induce persistent behavioral alterations in the rat.

NEUROBEHAVIOURAL FUNCTIONS IN ADULT PROGENY OF RAT MOTHERS EXPOSED TO METHYLMERCURY OR 2,2',4,4',5,5'-HEXACHLOROBIPHENYL (PCB 153) ALONE OR THEIR COMBINATION DURING GESTATION AND LACTATION

OBJECTIVES Methylmercury (MeHg) and polychlorinated biphenyls (PCBs) are ubiquitous environmental pollutants. Both are neurotoxic, especially for the developing brain. The main source of human exposure to MeHg and PCBs is seafood. The aim of the present work was to find out whether and how separate or combined perinatal exposure to these neurotoxicants affects neurobehavioural functions in maturity. MATERIALS AND METHODS The study was performed on adult Wistar rats, the progeny of rat mothers exposed to MeHg (0.5 mg/kg/day or 2.0 mg/kg/day), PCB 153 (1.0 mg/kg/day or 5.0 mg/kg/day), or to MeHg 0.5 mg/kg/day + PCB 153 5.0 mg/kg/day, from day 7 of pregnancy to day 21 post partum. The following functions were assessed: spontaneous locomotor activity (open field test), spatial short-term memory (radial maze test), long-term memory (passive avoidance test), sensitivity to pain and vulnerability to stress (hot plate test), efficiency of the sensorimotor gating (startle response test), and sensorimotor coordination (the rotarod test). RESULTS The results obtained in the MeHg part of the study showed a reduced locomotor activity in the female progeny of both exposed groups, an impaired passive avoidance in the male progeny of the high and low exposure group and a faster recovery from the effects of the stressful experience (hot plate test) in the male progeny of the high dose group. Results obtained in the PCB part showed an increased locomotor activity in the female progeny of both exposure groups and impairment in rotarod performance in males of the high dose group. Neurobehavioural alterations were not found in either the females or males exposed jointly to MeHg and PCB 153. CONCLUSIONS The results suggest that in condition of the combined exposure, MeHg may protect against the effects of PCB 153 and vice versa.

Behavioral effects following repeated exposure to hexachloronaphthalene in rats.

Polychlorinated naphthalenes (PCNs), including hexachloronaphthalene (HxCN), are widespread global environmental contaminants. Our experiments were aimed at assessing HxCN effects on motor behavior, long-term memory, pain sensitivity, magnitude of stress-induced analgesia, auditory function and sensorimotor gating, following repeated intragastric administration (28 days) of HxCN at 0.3 and 1.0 mg/kg body weight. Three weeks after the exposure termination, male Wistar rats were subjected to the neurobehavioral tests battery performed in the following order: open-field test, passive avoidance test, hot-plate test and acoustic startle response test. Repeated administration of HxCN induced disorders of motivational processes manifested by: anorectic effect caused by aphagia and adipsia; significantly reduced motor activity (hypokinesia); impaired long-term memory and acquired passive avoidance reaction; reduced pain threshold and shortened duration of anxiety reaction after pain stimulus (sensory neglect). Some of these neurobehavioral effects (impaired long-term memory, reduced pain threshold and stress-induced analgesia) were observed at 0.3 mgHxCN/kg body weight without any signs of overt toxicity. The outcome of our study shows that HxCN, like other compounds of the persistent organic pollutants (POPs) group, creates a potential risk of behavioral changes in the central nervous system in the general population as a result of environmental exposure.

Alteration in behavioral sensitivity to amphetamine after treatment with oxotremorine. Effect of dose and test environment.

Our earlier experiment revealed that rats pretreated once with an anticholinesterase develop hyposensitivity to amphetamine (AMPH). One of the likely causes of this effect might be a transient hyperexcitation of the central muscarinic receptors. It has appeared, however, that rats pretreated with oxotremorine (OX), a muscarinic agonist, show an augmented behavioral response to AMPH weeks later. The present experiments were performed in order to obtain more information on the relationship between the OX-induced sensitization to AMPH and the OX dose and dosing regime (single or repeated), and to find out whether the environment associated with the acute effects of OX could affect the response to AMPH. In experiment 1, adult male rats were given a single i.p. injection of OX in home cages at a moderate (0.5 mg/kg) or high (1.0 mg/kg) dose. In experiment 2, the rats received eight 1.0 mg/kg doses of OX in the course of three days. After each injection, some animals returned to their home cages, and some were placed in the test cages for 30 min. In both experiments, the response to AMPH was assessed on day 21 after the treatment. The obtained results indicate that: (i) a single i.p. exposure to OX results in an increase of the rats behavioral sensitivity to AMPH but the moderate dose is more effective in inducing this effect; (ii) repeated exposure to OX at high doses, in a regime enabling development of tolerance to the acute OX effects, does not alter the rat sensitivity to AMPH, and (iii) expression of the AMPH response is suppressed in environment which has been associated with acute effects of OX.

Neuroendocrine and behavioral response to amphetamine challenge after exposure to an organophosphorus pesticide

ObjectivesExposure to various stressors is known to result in sensitization to psychostimulants, a state related to the psychostimulant dependence and addiction. It has been shown in some studies that the rise in corticosterone (CORT) concentration is indispensable for both the induction and the expression of behavioral sensitization. Therefore, it might be suspected that behavioral hyposensitivity to amphetamine (AMPH) is somehow related to a reduced CORT response to the psychostimulant subsequent to the chlorphenvinphos (CVP) intoxication.Materials and MethodsThe male adult Wistar rats received single i.p. injections of CVP at the doses 0.5, 1.0 or 3.0 mg/kg b.w., or pure corn oil. CORT concentration was determined in samples of blood drawn from the tail vein before and then 30, 60, 180 min and 24 h after injection. The other rats were divided into two groups and tested, three weeks after the CVP injection for the effect of AMPH (0.5 mg/kg b.w. i.p.) on the serum CORT concentration. In addition, behavioral sensitivity to AMPH was assessed by measuring locomotor activity of the animals in an open-field.Results1) The stressor property of CVP was confirmed. The injection resulted in up to tenfold increase in the serum CORT concentration. The magnitude and duration of this response were dose-related. 2) Three weeks after the CVP exposure, the CORT response to AMPH was significantly increased. 3) The behavioral response to the psychostimulant, i.e. augmented locomotion, was significantly reduced compared to the control.ConclusionsThe results confirm that CVP exposure causes behavioral hyposensitivity to AMPH. This effect, however, could not be ascribed to a diminished CORT response.