Cerebellar neurotransmission in attention-deficit/hyperactivity disorder: does dopamine neurotransmission occur in the cerebellar vermis?
Children and adolescents with attention-deficit/hyperactivity disorder (ADHD) have smaller cerebellar volumes, particularly in the posterior-inferior cerebellar vermis (lobules VIII-X). Functional activation of the human cerebellar vermis following stimulant administration has also been repeatedly demonstrated. There is no well-characterized dopaminergic pathway that projects to the posterior-inferior cerebellar vermis, although the dopamine transporter (DAT) and tyrosine hydroxylase (TH) have been localized in the posterior-inferior vermis in the non-human primate by immunohistochemistry. We hypothesized that DA neurotransmission may occur in localized "hot spots" in the cerebellar vermis, and if so, that differences in such neurotransmission might be relevant to the pathophysiology of ADHD. To investigate this hypothesis, cerebellar tissue was obtained from rats and non-human primates. Catecholamines were extracted and analyzed using HPLC with coulometric detection. A regional gradient of norepinephrine (NE) and DA was found throughout the cerebellum with NE levels always roughly 10-40-fold higher than DA in both rats and monkeys. In addition, in vivo microdialysis studies were performed in the rat posterior-inferior cerebellar vermis in anesthetized animals. Significant NE overflow was observed over baseline following reverse microdialysis induced release by potassium or d-amphetamine. DA overflow was not observed over baseline for potassium stimulation, but was significant for d-amphetamine stimulation. These studies refute the hypothesis that DA neurotransmission normally occurs in the rat cerebellar vermis, but highlight that vermal DA is released by d-amphetamine. The presence of DAT may therefore allow for enhanced regulation of NE and not regulation of released DA.
Glaser
Paul E A
PE
Department of Psychiatry, University of Kentucky Chandler Medical Center, Lexington, 40536, USA. pglas0@uky.edu
Surgener
Stewart P
SP
Grondin
Richard
R
Gash
C R
CR
Palmer
Mike
M
Castellanos
F Xavier
FX
Gerhardt
Greg A
GA
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D001289:Attention Deficit Disorder with Hyperactivity / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology*; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D006719:Homovanillic Acid / Q000378:metabolism; D008253:Macaca mulatta; D008297:Male; D017551:Microdialysis / Q000379:methods; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D013997:Time Factors
D015102:3,4-Dihydroxyphenylacetic Acid; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine; D009638:Norepinephrine; D006719:Homovanillic Acid