Effects of Perinatal MeHg and/or 2, 2,' 4, 4,' 5, 5'- Hexachlorobiphenyl (PCB153) Exposure on Adult Vulnerability to Amphetamine in Rats

摘要

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 (CH_3HgCl) 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:rn1) before a sensitization treatment in order to assess the rat's "normal" sensitivity to the psychostimulant, andrn2) 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.