Behavioral and neurochemical sensitization to amphetamine following early postnatal administration of methylmercury (MeHg).
Perinatal exposure to methylmercury (MeHg) in rodents has been linked to changes in sensitivity to dopaminergic agents later in life. In an effort to determine the behavioral and neurochemical response to the indirect dopaminergic and serotonergic agonist amphetamine following neonatal exposure to MeHg, male BALB/c mice were administered MeHg during critical periods of neural development and challenged with amphetamine as adults. Mice were observed 15, 30 and 60 min after a single amphetamine injection (7.5 mg/kg i.p.) for presence of stereotypic and self-injurious behaviors, abnormal posture, and hyperthermia. Mice treated with 2 or 4 mg/kg MeHg on alternate days 3-15 of life demonstrated an increase in body temperature and the appearance of stereotypic and self-injurious behaviors not observed when amphetamine was administered to either vehicle-exposed mice or those treated with an equivalent total amount of MeHg administered on postnatal days 13 and 15. Neurochemical analysis of MeHg- and vehicle-exposed mice challenged with amphetamine or saline revealed alterations in dopaminergic and serotonergic activity which corresponded to the sensitized behavioral response to amphetamine. These observations demonstrate a critical window for MeHg exposure affecting the later appearance of amphetamine-induced self-injurious behavior and support the hypothesis that early exposure to environmental neurotoxicants may predispose individuals to engage in aberrant, intrusive behaviors later in life.
Wagner
George C
GC
Department of Pharmacology and Toxicology, Rutgers University, New Brunswick, NJ 08854, United States. gcwagner@rci.rutgers.edu
Reuhl
Kenneth R
KR
Ming
Xue
X
Halladay
Alycia K
AK
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000661:Amphetamine / Q000633:toxicity*; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001522:Behavior, Animal / Q000187:drug effects*; D001831:Body Temperature / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects*; D000697:Central Nervous System Stimulants / Q000633:toxicity*; D004032:Diet; D004298:Dopamine / Q000378:metabolism; D005260:Female; D006719:Homovanillic Acid / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008767:Methylmercury Compounds / Q000633:toxicity*; D051379:Mice; D008807:Mice, Inbred BALB C; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism; D011187:Posture; D017397:Prefrontal Cortex / Q000378:metabolism; D011247:Pregnancy; D016728:Self-Injurious Behavior / Q000139:chemically induced; D012701:Serotonin / Q000378:metabolism; D013239:Stereotyped Behavior / Q000187:drug effects
D000697:Central Nervous System Stimulants; D008767:Methylmercury Compounds; D015102:3,4-Dihydroxyphenylacetic Acid; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D000661:Amphetamine; D004298:Dopamine; D006719:Homovanillic Acid