title: 9-Methyl-β-carboline-induced cognitive enhancement is associated with elevated hippocampal dopamine levels and dendritic and synaptic proliferation.
abstract: β-Carbolines (BCs) belong to the heterogenous family of carbolines, which have been found exogenously, that is, in various fruits, meats, tobacco smoke, alcohol and coffee, but also endogenously, that is, blood, brain and CSF. These exogenous and endogenous BCs and some of their metabolites can exert neurotoxic effects, however, an unexpected stimulatory effect of 9-methyl-β-carboline (9-me-BC) on dopaminergic neurons in primary mesencephalic cultures was recently discovered. The aim of the present study was to extend our knowledge on the stimulatory effects of 9-me-BC and to test the hypothesis that 9-me-BC may act as a cognitive enhancer. We found that 10 days (but not 5 days) of pharmacological treatment with 9-me-BC (i) improves spatial learning in the radial maze, (ii) elevates dopamine levels in the hippocampal formation, and (iii) results after 10 days of treatment in elongated, more complex dendritic trees and higher spine numbers on granule neurons in the dentate gyrus of 9-me-BC-treated rats. Our results demonstrate that beyond its neuroprotective/neurorestorative and anti-inflammatory effects, 9-me-BC acts as a cognitive enhancer in a hippocampus-dependent task, and that the behavioral effects may be associated with a stimulatory impact on hippocampal dopamine levels and dendritic and synaptic proliferation.
authors.affiliation: Otto von Guericke University Magdeburg, Institute of Biology, Magdeburg, Germany. michael.gruss@ovgu.de
authors.forename: Michael
authors.initials: M
authors.lastname: Gruss
authors.forename: Dorothea
authors.initials: D
authors.lastname: Appenroth
authors.forename: Armin
authors.initials: A
authors.lastname: Flubacher
authors.forename: Christoph
authors.initials: C
authors.lastname: Enzensperger
authors.forename: Jörg
authors.initials: J
authors.lastname: Bock
authors.forename: Christian
authors.initials: C
authors.lastname: Fleck
authors.forename: Gabriele
authors.initials: G
authors.lastname: Gille
authors.forename: Katharina
authors.initials: K
authors.lastname: Braun
mesh_terms: D000818:Animals; D002243:Carbolines / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D003071:Cognition / Q000187:drug effects*; D003712:Dendrites / Q000187:drug effects*; D004298:Dopamine / Q000378:metabolism; D005260:Female; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D018782:Maze Learning / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013569:Synapses / Q000187:drug effects*
chemical_list: C529608:9-methyl-beta-carboline; D002243:Carbolines; D000697:Central Nervous System Stimulants; D004298:Dopamine