title: Juvenile exposure to methylphenidate reduces cocaine reward and alters netrin-1 receptor expression in adulthood.
abstract: The guidance cue netrin-1 acting on mesocorticolimbic dopamine (DA) neurons through its receptor DCC (deleted in colorectal cancer) has been implicated in the neuronal plasticity induced by psychostimulant drugs. We examined in C57/BL6 mice the effects of repeated juvenile methylphenidate (MPH) exposure on cocaine-reward sensitivity in adulthood and determined whether early MPH treatment alters adult expression of DCC in mesocorticolimbic DA regions. By using place conditioning, we show that adult mice exposed to MPH during the juvenile period are less sensitive to cocaine-reward compared to saline-controls. Furthermore, by means of immunoblotting, we demonstrate that early MPH treatment attenuates adult DCC expression in the ventral tegmental area (VTA) selectively. These results support previous evidence that developmental MPH treatment diminishes cocaine-reward in adulthood and are the first to suggest that DCC in the VTA may participate in this enduring effect.
authors.affiliation: Department of Psychiatry, Douglas Mental Health University Institute, McGill University, 6875 LaSalle Boulevard, Montreal, Quebec, H4H 1R3, Canada.
authors.forename: Jessica K
authors.initials: JK
authors.lastname: Argento
authors.forename: Andreas
authors.initials: A
authors.lastname: Arvanitogiannis
authors.forename: Cecilia
authors.initials: C
authors.lastname: Flores
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D003042:Cocaine / Q000008:administration & dosage*; D003216:Conditioning, Operant / Q000187:drug effects; D003463:Cues; D000075389:DCC Receptor; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D008297:Male; D008774:Methylphenidate / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011956:Receptors, Cell Surface / Q000378:metabolism*; D012201:Reward; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000378:metabolism
chemical_list: D000075389:DCC Receptor; C501910:Dcc protein, mouse; D018765:Dopamine Uptake Inhibitors; D011956:Receptors, Cell Surface; D025521:Tumor Suppressor Proteins; D008774:Methylphenidate; D003042:Cocaine