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

Regul Pept. 2004 Dec 15;123(1-3):225-34. doi: 10.1016/j.regpep.2004.05.010.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Attention Deficit Disorder with Hyperactivity / physiopathology
  • Autistic Disorder / physiopathology
  • Benzhydryl Compounds
  • Brain / drug effects
  • Brain / physiology*
  • Dibutyl Phthalate / toxicity
  • Diethylhexyl Phthalate / toxicity
  • Dopamine / metabolism*
  • Endocrine Glands / drug effects
  • Gene Expression / drug effects
  • Humans
  • Male
  • Motor Activity / drug effects*
  • Motor Activity / physiology*
  • Nerve Growth Factors / physiology*
  • Neurons / drug effects
  • Neurons / metabolism*
  • Neuropeptides / physiology*
  • Neurotransmitter Agents / physiology*
  • Oxidopamine / toxicity
  • Phenols / toxicity
  • Pituitary Adenylate Cyclase-Activating Polypeptide
  • Rats
  • Rats, Wistar


  • ADCYAP1 protein, human
  • Adcyap1 protein, rat
  • Benzhydryl Compounds
  • Nerve Growth Factors
  • Neuropeptides
  • Neurotransmitter Agents
  • Phenols
  • Pituitary Adenylate Cyclase-Activating Polypeptide
  • Dibutyl Phthalate
  • nonylphenol
  • Oxidopamine
  • Diethylhexyl Phthalate
  • bisphenol A
  • Dopamine