GBR-12909-induced self-injurious behavior: role of dopamine.
A regimen of repeated administration of GBR (10 or 20 mg/kg/day, i.p., for 4 days) to female Sprague-Dawley rats induced a dose-and time-related increase in the incidence of self-injurious behavior (SIB) that consisted of injury to body areas, paws and tail. The treatment regimen decreased striatal DA and DOPAC levels. Dopaminergic denervation with 6-hydroxydopamine (6-OHDA) or D1 DA antagonist, SCH-23390 or D2 DA antagonist, spiperone, blocked the GBR-induced SIB. Male rats were less sensitive than female rats to exhibit a comparable incidence of SIB. Taken together, the study reveals that repeated administration of GBR induces SIB that is dependent on the integrity of nigrostriatal dopaminergic system and the presence of D1 and/or D2 DA receptors.
Department of Pharmacology and Toxicology, Northwest Center for Medical Education, Indiana University School of Medicine, Gary 46408, USA.
S P
SP
Sivam
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects*; D004298:Dopamine / Q000378:metabolism / Q000502:physiology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016728:Self-Injurious Behavior; D013134:Spiperone / Q000494:pharmacology; D013378:Substantia Nigra / Q000187:drug effects*
D001552:Benzazepines; D018492:Dopamine Antagonists; D018765:Dopamine Uptake Inhibitors; D010879:Piperazines; D015102:3,4-Dihydroxyphenylacetic Acid; D013134:Spiperone; C043425:vanoxerine; D004298:Dopamine