title: Motor hyperactivity caused by a deficit in dopaminergic neurons and the effects of endocrine disruptors: a study inspired by the physiological roles of PACAP in the brain.
abstract: Recent studies have revealed that the pituitary adenylate cyclase-activating polypeptide (PACAP) might act as a psychostimulant. Here we investigated the mechanisms underlying motor hyperactivity in patients with pervasive developmental disorders, such as autism, and attention-deficit hyperactivity disorder (ADHD). We studied the effects of intracisternal administration of 6-hydroxydopamine (6-OHDA) or endocrine disruptors (EDs) on spontaneous motor activity (SMA) and multiple gene expression in neonatal rats. Treatment with 6-OHDA caused significant hyperactivity during the dark phase in rats aged 4-5 weeks. Motor hyperactivities also were observed after treatment with endocrine disruptors, such as bisphenol A, nonylphenol, diethylhexyl phthalate and dibutyl phthalate, during both dark and light phases. Gene-expression profiles produced using cDNA macroarrays of 8-week-old rats with 6-OHDA lesions revealed the altered expression of several classes of gene, including the N-methyl-D-aspartate (NMDA) receptor 1, glutamate/aspartate transporter, gamma-aminobutyric-acid transporter, dopamine transporter 1, D4 receptor, and peptidergic elements such as the galanin receptor, arginine vasopressin receptor, neuropeptide Y and tachykinin 2. The changes in gene expression caused by treatment with endocrine disruptors differed from those induced by 6-OHDA. These results suggest that the mechanisms underlying the induction of motor hyperactivity and/or compensatory changes in young adult rats might differ between 6-OHDA and endocrine disruptors.
authors.affiliation: Human Stress Signal Research Center, National Institute of Advanced Industrial Science and Technology, Tsukuba Central 6, 1-1-1 Higashi, Tsukuba 305-8566, Japan. y-masuo@aist.go.jp
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Masuo
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Morita
authors.forename: Syuichi
authors.initials: S
authors.lastname: Oka
authors.forename: Masami
authors.initials: M
authors.lastname: Ishido
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001289:Attention Deficit Disorder with Hyperactivity / Q000503:physiopathology; D001321:Autistic Disorder / Q000503:physiopathology; D001559:Benzhydryl Compounds; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D003993:Dibutyl Phthalate / Q000633:toxicity; D004051:Diethylhexyl Phthalate / Q000633:toxicity; D004298:Dopamine / Q000378:metabolism*; D004702:Endocrine Glands / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008297:Male; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology*; D009414:Nerve Growth Factors / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009479:Neuropeptides / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000502:physiology*; D016627:Oxidopamine / Q000633:toxicity; D010636:Phenols / Q000633:toxicity; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D051381:Rats; D017208:Rats, Wistar; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D003993:Dibutyl Phthalate; D004051:Diethylhexyl Phthalate; D004298:Dopamine; D009414:Nerve Growth Factors; D009479:Neuropeptides; D018377:Neurotransmitter Agents; D016627:Oxidopamine; D010636:Phenols; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; C495401:ADCYAP1 protein, human; C495403:Adcyap1 protein, rat; C025256:nonylphenol; C006780:bisphenol A; D000098826:Bisphenol A Compounds