Administration of oral methylphenidate during adolescence prevents suppressive development of dopamine projections into prefrontal cortex and amygdala after an early pharmacological challenge in gerbils.
The enduring effects of postweaning subchronic methylphenidate (MP) treatment and/or previous early preweaning methamphetamine (MA) application on dopamine (DA) fiber density were investigated in multiple cortical and subcortical areas of the gerbil brain. The study aimed to explore three questions: (1) is the development of DA fiber innervation in control animals sensitive to a clinically relevant subchronic treatment with MP? (2) Is the development of DA fiber innervation in the forebrain altered by a single early MA challenge? (3) If so, might the subsequent institution of a therapeutically relevant MP application scheme interfere with such early induced alternative developmental trajectories for DA fiber innervation? For this purpose, gerbils pretreated both with saline and MA (50 mg/kg, i.p.) on day 14 received either H(2)O or MP (5 mg/kg) orally on days 30 to 60. On day 90, DA fibers were immunohistochemically detected and quantified. As a result, MP on its own did not have any significant influence on the postnatal development of the DA fiber systems, whereas it prevented a previously MA triggered suppressive development of DA fiber innervation in the prefrontal cortex and amygdala complex (30% less fiber innervation in both areas). Thus, MP prevented previously initiated miswiring of DA fibers from actually being implemented in the gerbil forebrain. During earlier studies, rather complex miswiring has been documented in response to an early preweaning MA challenge. This miswiring was associated with functional deficits resembling some of the symptoms of patients with ADHD. Therefore, morphogenetic properties of MP need further attention.
Grund
Thorsten
T
Department of Neuroanatomy, Faculty of Biology, University of Bielefeld, Bielefeld, Germany.
Teuchert-Noodt
Gertraud
G
Busche
Andrea
A
Neddens
Jörg
J
Brummelte
Susanne
S
Moll
Gunther H
GH
Dawirs
Ralph R
RR
D000284:Administration, Oral; D000375:Aging / Q000187:drug effects* / Q000502:physiology; D000679:Amygdala / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D000818:Animals; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D005849:Gerbillinae; D020439:Growth Cones / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D008774:Methylphenidate / Q000494:pharmacology*; D009434:Neural Pathways / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D055495:Neurogenesis / Q000187:drug effects / Q000502:physiology; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D017557:Ventral Tegmental Area / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism
D000697:Central Nervous System Stimulants; D008774:Methylphenidate