Cholecystokinin and GABA interaction in the dorsal hippocampus of rats in the elevated plus-maze test of anxiety.
In the present study, we have investigated the effects and interaction of CCK and GABAergic systems in the dorsal hippocampus of rats using the elevated plus-maze test of anxiety. Bilateral injection of different doses of CCK(8s) (0.01, 0.05 and 0.1 microg/rat) into the dorsal hippocampus (intra-CA1) decreased percentage of open arm time (%OAT) and open arm entries (%OAE) that are representative of anxiogenic-like behavior. The bilateral injection of three doses of LY225910, a selective CCK2 receptor antagonist (0.01, 0.1 and 0.5 microg/rat) produced significant anxiolytic behavior. Although muscimol (GABA(A+)) (0.1, 0.5 and 1 microg/rat, intra-CA1) produced dose dependent increase in %OAT and a slight increase in %OAE, bicuculline (GABA(A-)), (1, 2 and 4 microg/rat, intra-CA1) failed to change the anxiety profile. Both muscimol (0.1 microg/rat) and bicuculline (1 microg/rat), when co-administered with LY225910, reversed the effect of latter drug on anxiety but when co-administered with CCK8s (0.05 microg/rat) showed no effect on anxiety profile. In conclusion, it seems that both CCK and GABAergic systems not only play a part in the modulation of anxiety in the dorsal hippocampus of rats but also have demonstrated a complex interaction as well.
Rezayat
Mehdi
M
Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, P.O. Box 13145-784, Tehran, Iran. rezayat@sina.tums.ac.ir
Roohbakhsh
Ali
A
Zarrindast
Mohammad-Reza
MR
Massoudi
Roohollah
R
Djahanguiri
Bijan
B
D000818:Animals; D001007:Anxiety / Q000503:physiopathology*; D001640:Bicuculline / Q000494:pharmacology; D002766:Cholecystokinin / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D018756:GABA Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology*; D008297:Male; D008845:Microinjections; D011799:Quinazolines / Q000494:pharmacology; D052999:Quinazolinones; D051381:Rats; D017208:Rats, Wistar; D043887:Receptor, Cholecystokinin B / Q000378:metabolism; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors / Q000378:metabolism; D013238:Stereotaxic Techniques; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
C435663:2-(2-(5-bromo-1H-indol-3-yl)ethyl)-3-(1-methylethoxyphenyl)-4-(3H)-quinazolinone; D018756:GABA Antagonists; D011799:Quinazolines; D052999:Quinazolinones; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin; D005680:gamma-Aminobutyric Acid; D002766:Cholecystokinin; D001640:Bicuculline