Neonatal methamphetamine-induced corticosterone release in rats is inhibited by adrenal autotransplantation without altering the effect of the drug on hippocampal serotonin.
Rat neonatal methamphetamine exposure results in corticosterone release and learning and memory impairments in later life; effects also observed after neonatal stress. Previous attempts to test the role of corticosterone release after methamphetamine using corticosterone inhibitors were unsuccessful and adrenalectomy caused reductions in hippocampal serotonin greater than those caused by methamphetamine alone. Here we tested whether adrenal autotransplantation could be used to attenuate methamphetamine-induced corticosterone release without also altering the effects of the drug on serotonin. Adrenal autotransplantation surgery occurred on postnatal day 9 followed by methamphetamine or saline treatment from postnatal day 11-20 (10mg/kg/dosex4/day). Plasma corticosterone and hippocampal serotonin and 5-hydroxyindoleacetic acid were determined 30min following the first treatment on each day between postnatal days 11-20. Adrenal autotransplantation attenuated neonatal methamphetamine-induced corticosterone release by approximately 70% initially, approximately 55% midway through treatment, and approximately 25% by the end of treatment. Methamphetamine reduced serotonin and 5-hydroxyindoleacetic acid in the hippocampus in the ADXA rats to the same degree as in SHAM rats. The data show that neonatal adrenal autotransplantation is an effective method for partially reducing treatment-induced corticosterone release while providing sufficient corticosterone to sustain normal growth and development. The method should be applicable to other models of developmental stress/corticosterone release.
Division of Neurology, Dept. of Pediatrics, Cincinnati Children's Research Foundation, 3333 Burnet Ave., Cincinnati, OH 45229-3039, United States.
Curtis E
CE
Grace
Tori L
TL
Schaefer
Gary A
GA
Gudelsky
Michael T
MT
Williams
Charles V
CV
Vorhees
D000311:Adrenal Glands / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism / Q000637:transplantation*; D000818:Animals; D000831:Animals, Newborn; D000697:Central Nervous System Stimulants / Q000633:toxicity*; D002851:Chromatography, High Pressure Liquid; D003345:Corticosterone / Q000097:blood*; D005260:Female; D006624:Hippocampus / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D008297:Male; D008694:Methamphetamine / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism*; D014182:Transplantation, Autologous
D000697:Central Nervous System Stimulants; D012701:Serotonin; D008694:Methamphetamine; D003345:Corticosterone