Cholinergic and dopaminergic mechanisms involved in the recovery of circadian anticipation by aniracetam in aged rats.
We have reported that repeated administration of aniracetam (100 mg/kg p.o.) for 7 consecutive days recovers mealtime-associated circadian anticipatory behavior diminished in aged rats. The present study examines the mode of action underlying the restoration by aniracetam with various types of receptor antagonists. Coadministration of scopolamine (0.1 mg/kg i.p.) or haloperidol (0.1 mg/kg i.p.) for the last 3 days significantly reduced the restorative effects of aniracetam without affecting the timed feeding-induced anticipatory behavior by each receptor antagonist itself. The other receptor antagonists, mecamylamine (3 mg/kg i.p.), 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline (NBQX, 1 microg/rat i.c.v.) had no effect on either the basal or aniracetam-elicited circadian anticipation. In contrast, ketanserin (1 mg/kg i.p.) itself recovered the diminished anticipatory behavior as aniracetam did, but it did not alter the restorative effects of aniracetam. Among the receptor antagonists tested, NBQX reduced appetite and haloperidol induced circadian hypoactivity. These results suggest that the food-entrainable circadian oscillations or the temporal regulatory system of behavior is modulated by cholinergic, dopaminergic and serotonergic systems. Furthermore, aniracetam may restore the aging-diminished behavioral anticipation by activating muscarinic acetylcholine (ACh) and/or dopamine (DA) D2 receptors through the enhanced release of ACh and/or DA in the brain.
Tanaka
Yushiro
Y
CNS Supporting Laboratory, Nippon Roche Research Center, 200 Kajiwara, Kamakura, Kanagawa 247-8530, Japan.
Kurasawa
Mitsue
M
Nakamura
Kazuo
K
D000375:Aging / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D002940:Circadian Rhythm / Q000187:drug effects / Q000502:physiology*; D003624:Darkness; D008029:Lighting; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology*; D011760:Pyrrolidinones / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011950:Receptors, Cholinergic / Q000502:physiology*; D011954:Receptors, Dopamine / Q000502:physiology*
D011760:Pyrrolidinones; D011950:Receptors, Cholinergic; D011954:Receptors, Dopamine; C036466:aniracetam