Ondansetron, an antagonist of 5-HT3 receptors, antagonizes the anti-exploratory effect of caerulein, an agonist of CCK receptors, in the elevated plus-maze.
Systemic treatment with caerulein (0.25-5 micrograms/kg SC), non-selective agonist of cholecystokinin (CCK) receptors, dose-dependently suppressed the exploratory behaviour of rats in an elevated plus-maze without producing remarkable changes in the locomotor activity of animals in an open field test. Ondansetron, a selective antagonist of 5-HT3 receptors, increased the number of open arm entries in the plus-maze test only at a dose 10 micrograms/kg. The other doses of ondansetron (0.1, 1 and 100 micrograms/kg IP) did not significantly change either the locomotor activity or the exploratory behaviour of rats. Pretreatment of rats with ondansetron (at 10 micrograms/kg, but not at 0.1, 1 or 100 micrograms/kg) completely reversed the anti-exploratory effect of caerulein (5 micrograms/kg). The concomitant treatment with caerulein and ondansetron did not cause any major change in the locomotor activity of animals in open field. Consequently, we propose that 5-HT-ergic mechanisms are involved not only in the regulation of CCK release in the cerebral cortex and nucleus accumbens, but also in the modulation of the anti-exploratory effect of caerulein, a CCK agonist, in the elevated plus-maze.
Vasar
E
E
Department of Physiology, Tartu University, Estonia.
Peuranen
E
E
Oöpik
T
T
Harro
J
J
Männistö
P T
PT
D000818:Animals; D001007:Anxiety / Q000523:psychology*; D002108:Ceruletide / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005106:Exploratory Behavior / Q000187:drug effects*; D005260:Female; D009043:Motor Activity / Q000187:drug effects; D017294:Ondansetron / Q000494:pharmacology*; D051381:Rats; D011949:Receptors, Cholecystokinin / Q000819:agonists*; D012702:Serotonin Antagonists / Q000494:pharmacology*
D011949:Receptors, Cholecystokinin; D012702:Serotonin Antagonists; D017294:Ondansetron; D002108:Ceruletide