Aniracetam enhances glutamatergic transmission in the prefrontal cortex of stroke-prone spontaneously hypertensive rats.
The effects of aniracetam, a cognition enhancer, on extracellular levels of glutamate (Glu), gamma-aminobutyric acid (GABA) and nitric oxide metabolites (NOx) were examined in the prefrontal cortex (PFC) and the basolateral amygdala (AMG) in stroke-prone spontaneously hypertensive rats (SHRSP) using in vivo microdialysis. Basal release of Glu, was lower in the AMG of SHRSP than in normotensive Wistar Kyoto rats, whereas no difference in GABA and NOx was noted. Aniracetam (100 mg/kg, p.o.) significantly increased the area under the curve of Glu levels in the PFC, but not in the AMG, of SHRSP. Aniracetam failed to exert any remarkable effects on GABA or NOx levels in either brain region. Our findings suggest that aniracetam enhances cortical glutamatergic release, which may be the mechanism involved in the ameliorating effects of aniracetam on various neuronal dysfunctions.
Togashi
Hiroko
H
Department of Pharmacology, Hokkaido University Graduate School of Medicine, Kita-15, Nishi-7, Kita-ku, Sapporo 060-8638, Japan. thiro@med.hokudai.ac.jp
Nakamura
Kazuo
K
Matsumoto
Machiko
M
Ueno
Ken-ichi
K
Ohashi
Satoshi
S
Saito
Hideya
H
Yoshioka
Mitsuhiro
M
D000596:Amino Acids / Q000378:metabolism; D000679:Amygdala / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D002544:Cerebral Infarction / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D020925:Hypoxia-Ischemia, Brain / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D017551:Microdialysis; D009569:Nitric Oxide / Q000378:metabolism; D018697:Nootropic Agents / Q000494:pharmacology*; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D011760:Pyrrolidinones / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D020521:Stroke / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D000596:Amino Acids; D018697:Nootropic Agents; D011760:Pyrrolidinones; D009569:Nitric Oxide; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; C036466:aniracetam