Effects of the 5-HT1B receptor antagonist NAS-181 on extracellular levels of acetylcholine, glutamate and GABA in the frontal cortex and ventral hippocampus of awake rats: a microdialysis study.
The purpose of this study was to investigate the effects of the 5-HT(1B) receptor antagonist NAS-181 ((R)-(+)-2-(3-morpholinomethyl-2H-chromen-8-yl) oxymethyl-morpholine methanesulfonate) on cholinergic, glutamatergic and GABA-ergic neurotransmission in the rat brain in vivo. Extracellular levels of acetylcholine, glutamate and GABA were monitored by microdialysis in the frontal cortex (FC) and ventral hippocampus (VHipp) in separate groups of freely moving rats. NAS-181 (1, 5 or 10 mg/kg, s.c.) caused a dose-dependent increase in ACh levels, reaching the maximal values of 500% (FC) and 230% (VHipp) of controls at 80 min post-injection. On the contrary, NAS-181 injected at doses of 10 or 20 mg/kg s.c. had no effect on basal extracellular levels of Glu and GABA in these areas. The present data suggest that ACh neurotransmission in the FC and VHipp, the brain structures strongly implicated in cognitive function, is under tonic inhibitory control of 5-HT(1B) heteroreceptors localized at the cholinergic terminals in these areas.
Hu
Xiao Jing
XJ
Department of Neuroscience, Retzius väg 8, Karolinska Institutet, SE-171 77, Stockholm, Sweden.
Wang
Fu-Hua
FH
Stenfors
Carina
C
Ogren
Sven Ove
SO
Kehr
Jan
J
D000109:Acetylcholine / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology*; D001923:Brain Chemistry / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D045604:Extracellular Fluid / Q000187:drug effects* / Q000378:metabolism; D005625:Frontal Lobe / Q000187:drug effects*; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects*; D008297:Male; D017551:Microdialysis / Q000379:methods; D009025:Morpholines / Q000494:pharmacology*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012702:Serotonin Antagonists / Q000494:pharmacology*; D014851:Wakefulness; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
C112429:2-(((3-(morpholinylmethyl)-2H-chromen-8-yl)oxy)methyl)morpholine; D001578:Benzopyrans; D009025:Morpholines; D018377:Neurotransmitter Agents; D012702:Serotonin Antagonists; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D000109:Acetylcholine