title: Sex and dose-related differences in methylphenidate adolescent locomotor sensitization and effects on brain-derived neurotrophic factor.
abstract: This study analyzed repeated methylphenidate (MPH) administration and its effects on brain-derived neurotrophic factor (BDNF) in the dorsal striatum and nucleus accumbens of male and female adolescent rats. In Experiment 1, rats were administered intraperitoneal (ip) saline, 1, 3, or 5 mg/kg dose of MPH every second day from postnatal day (P)33-P49. Locomotor activity was analyzed for 10 min after each administration. Results revealed that the 1 mg/kg dose of MPH produced locomotor suppression, however, the 5 mg/kg dose of MPH produced locomotor sensitization and robust behavioral activation in females as compared to males. In Experiment 2, animals were administered ip saline or the 5 mg/kg dose of MPH using an identical regimen but a 30 min behavioral test was employed. Dorsal striatum and nucleus accumbens tissue was assayed for BDNF at P50. Females demonstrated sensitization to MPH and increased locomotor activation compared to males. Interestingly, females given MPH demonstrated a significant 42% decrease of striatal BDNF whereas males administered MPH demonstrated a significant 50.4% increase of striatal BDNF compared to controls. There were no effects on accumbal BDNF. This report demonstrates robust sex differences in the behavioral response, but sex-dependent changes in striatal BDNF in response to MPH in adolescence.
authors: Department of Psychology, East Tennessee State University, Johnson City, TN 37614, USA. brown1@mail.etsu.edu
authors: Russell W
authors: RW
authors: Brown
authors: Benjamin A
authors: BA
authors: Hughes
authors: Andrew B
authors: AB
authors: Hughes
authors: A Brianna
authors: AB
authors: Sheppard
authors: Marla K
authors: MK
authors: Perna
authors: W Lee
authors: WL
authors: Ragsdale
authors: Ross L
authors: RL
authors: Roeding
authors: Brooks B
authors: BB
authors: Pond
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D008774:Methylphenidate / Q000008:administration & dosage / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012737:Sex Factors
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D018765:Dopamine Uptake Inhibitors; D008774:Methylphenidate