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Methylmercury (MeHg) and polychlorinated biphenyls (PCBs) are ubiquitous and persistent environmental pollutants and known neurotoxicants. It has been recognized that dietary exposure to neurotoxic substances during pregnancy and breast feeding may affect the development of the child’s nervous system and result in various neurological and neurobehavioural alterations later in life. One of the suspected consequences of such exposure may be an increased propensity to psychostimulant abuse and psychostimulant addiction. Data from animal studies indicate that behavioural sensitivity to psychostimulants is a good predictor of the propensity to psychostimulant self-administration – an animal model of drug abuse in humans. The aim of this study was to find out whether and how perinatal exposure to MeHg and/or PCB153 determines behavioural sensitivity and sensitizability to the psychostimulant amphetamine (AMPH) in adulthood. The subjects were adult rats, Wistars, born to mothers exposed, via drinking water, to MeHg (CH₃HgCl) at 0.5 mg/kg/day; or PCB153 (2,2’,4,4’,5,5’-hexachlorobiphenyl) at 5.0 mg/kg/day by gavage, or jointly MeHg (0.5 mg/kg/day, and PCB153 (5.0 mg/kg/day), from day 7 of pregnancy to day 21 post partum. The testing started at the age of 3 months. It consisted in measuring the behavioural response to a test dose of AMPH (0.5 mg/kg. i.p.) twice: 1) before a sensitization treatment in order to assess the rat’s “normal” sensitivity to the psychostimulant, and 2) three weeks after the sensitizing treatment. The sensitization treatment consisted in a repeated (once a day for five consecutive days) administration of AMPH at 2.5 mg/kg. Results: 1) Before the sensitization treatment there were no differences between the exposed and the control rats in the response to the psychostimulant. 2) Three weeks after the sensitizing treatment the response to an AMPH challenge was increased in all rats. However, in males exposed perinatally to MeHg alone, this increase was significantly more pronounced than in males of the control group. A similar effect was not present in MeHg-exposed females as well as males or females exposed to PCB153 alone or in combination with MeHg. Perinatal exposure to MeHg may result in an increased susceptibility to psychostimulant sensitization in the male progeny. Co- exposure to PCB153 may compromise this effect of MeHg-exposure.
The vulnerability of the nervous system to toxic insult is particularly high during foetal life and early childhood. Exposures during this period, via maternal blood and/or milk, may result in neurobehavioural disorders, some of which may not become apparent before in adulthood. Methylmercury (MeHg) and polychlorinated biphenyls (PCB) are persistent environmental pollutants and may be present in some food products. Both are neurotoxic. It is suspected that MeHg and PCBs may act synergistically in inducing neurotoxic effects. Some data suggest that catecholaminergic systems, especially the dopaminergic one, are particularly vulnerable to the harmful action of MeHg and PCBs. This study aimed to assess the influence of separate or combined perinatal exposure to MeHg and PCB 153 on brain catecholamine contents in maturity. The subjects were adult (90-94 days of age) rats, progeny of mothers exposed to methylmercury (MeHg, CH₃HgCl) or 2,2’,4,4’,5,5’-hexachlorobiphenyl (PCB 153), or MeHg and PCB 153, from day 7 of gestation to day 21 post partum. MeHg was administered with drinking water at daily doses of 0.5 mg/kg b.w./day. PCB 153 was administered by gavage at daily doses of 5 mg/kg b.w./day. The concentrations of adrenaline (A), noradrenaline (NA), dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) were determined by HPLC in homogenates of the following brain regions: olfactory bulb, hippocampus, striatum, occipito-temporal cortex, diencephalon, mesencephalon and cerebellum. The results suggest some exposure-related alterations in amine contents and point to the significant role of gender in their development. In the female MeHg-exposed progeny, the content of NA, DA and DOPAC in the mesencephalon was significanrtly elevated (by 43.1, 68.9 and 65.1%, respectively) while in the male progeny no differences were noted in any region of the brain. On the other hand, in the progeny exposed to PCB 153, some differences, i.e. increased NA concentration in the olfactory bulb (by 59.9%) and hippocampus (by 124.5%) and increased DA (by 75.0%) in the striatum were found in males, whereas in females significant differences were not found. In the case of combined exposure, the data suggest some effects in the female progeny only: a decreased concentration of A in the hippocampus (by 40.9%) but increased in the stratum (by 53.1%) and an increased DA concentration in the mesencephalon (by 78.9%). Summing up, the results confirm that gender may be an important determinant of the rat’s vulnerability to MeHg and PCB153. They provide no evidence, however, of a synergism in the action of these neurotoxicants when given perinatally on the brain catecholaminergic systems in adulthood. A rough analysis of the obtained data allows one to suspect an antagonistic rather than synergistic type of interaction.
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