Impulsivity and AMPA receptors: aniracetam ameliorates impulsive behavior induced by a blockade of AMPA receptors in rats.
The study aimed to ascertain the involvement of central AMPA receptors in impulsive behaviors of aged rats and to examine the effects of aniracetam. Premature response in the two-lever choice reaction task was assessed as an index of impulsivity. Intracerebroventricular injection of 2, 3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline (NBQX), an AMPA receptor antagonist, dose-dependently (10.1-1009 ng/rat) increased only premature response without altering responding speed and choice accuracy 30 min after the injection. Aniracetam (30 mg/kg p.o.), a positive allosteric modulator of AMPA receptors, or AMPA (55.9 ng/rat, co-injected with NBQX) completely restored the NBQX-induced increase in impulsivity. These results indicate that AMPA receptors are tonically involved in the regulation of impulsivity.
Nakamura
K
K
CNS Supporting Laboratory, Nippon Roche Research Center, 200 Kajiwara, Kamakura, Japan. kazuo.nakamura.@roche.com
Kurasawa
M
M
Shirane
M
M
D000818:Animals; D001007:Anxiety / Q000188:drug therapy; D001522:Behavior, Animal / Q000187:drug effects*; D003216:Conditioning, Operant / Q000187:drug effects; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D007175:Impulsive Behavior / Q000378:metabolism*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D018697:Nootropic Agents / Q000494:pharmacology*; D011760:Pyrrolidinones / Q000494:pharmacology*; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000819:agonists / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018697:Nootropic Agents; D011760:Pyrrolidinones; D011810:Quinoxalines; D018091:Receptors, AMPA; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; C036466:aniracetam; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid