title: Anxiogenic effect of CCK8s in the ventral hippocampus of rats: possible involvement of GABA(A) receptors.
abstract: Cholecystokinin (CCK) as an important neuropeptide in the brain has been implicated in the modulation of anxiety. The effects of this neurotransmitter on anxiety-like behavior in the ventral hippocampus have not been evaluated yet. Moreover, some evidences show a functional interaction between GABA and CCK in the nervous system. Bilateral injections of three doses of CCK8s (0.01, 0.05 and 0.1 μg/rat) into the ventral hippocampus decreased percentage of open arm time (%OAT) and open arm entries (%OAE) that are representative of anxiogenic-like behavior in the elevated plus-maze test of anxiety. Bilateral injections of LY225910, a selective CCK(2) receptor antagonist, at the doses of 0.01, 0.1 and 0.5 μg/rat did not change anxiety-related parameters. Administration of muscimol, a selective GABA(A) receptor agonist, at the doses of 0.001, 0.005 and 0.01 μg/rat produced dose dependent increase in %OAT and %OAE indicating an anxiolytic-like effect, while administration of bicuculline, a selective GABA(A) receptor antagonist, at the doses of 0.1, 0.2 and 0.5 μg/rat decreased %OAT and %OAE showing that this drug promoted anxious behavior of the rats. Co-administration of bicuculline (0.2 μg/rat) with CCK8s decreased the anxiogenic effects of CCK8s. Furthermore, co-administration of LY225910 (0.5 μg/rat) with muscimol increased the anxiolytic effect of muscimol at the dose of 0.001 μg/rat. The results of this study suggest that both CCK and GABAergic system have important and opposite roles in the modulation of anxiety-like behavior in the ventral hippocampus of rats and they may have a complex interaction in the ventral hippocampus to modulate anxiety-related behavior.
authors.affiliation: Department of Biology, University of Mazandaran, Pasdaran Street, Babolsar, P.O. Box 47416-13534, Iran. a.hajizadeh@umz.ac.ir
authors.forename: Akbar
authors.initials: A
authors.lastname: Hajizadeh Moghaddam
authors.forename: Robabeh Sadat
authors.initials: RS
authors.lastname: Hosseini
authors.forename: Ali
authors.initials: A
authors.lastname: Roohbakhsh
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001007:Anxiety / Q000188:drug therapy / Q000378:metabolism; D001522:Behavior, Animal / Q000187:drug effects*; D002766:Cholecystokinin / Q000378:metabolism / Q000494:pharmacology*; D018756:GABA Antagonists / Q000494:pharmacology; D058785:GABA-A Receptor Agonists / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D052999:Quinazolinones / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: C435663:2-(2-(5-bromo-1H-indol-3-yl)ethyl)-3-(1-methylethoxyphenyl)-4-(3H)-quinazolinone; D014151:Anti-Anxiety Agents; D018756:GABA Antagonists; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D052999:Quinazolinones; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; D002766:Cholecystokinin