Anxiogenic-like action of caerulein, a CCK-8 receptor agonist, in the mouse: influence of acute and subchronic diazepam treatment.
Effects of caerulein, a cholecystokinin octapeptide (CCK-8) receptor agonist, on exploratory activity of mice were investigated. Exploratory and locomotor activity of animals were measured using elevated plus-maze and open field tests. The systemic administration of caerulein at non-sedative doses (100 ng/kg-1 micrograms/kg i.p.) resulted in a significant decrease in the exploratory activity of mice. This effect was completely blocked by proglumide, a CCK-8 receptor. Acute treatment with low doses (0.1-0.75 mg/kg i.p.) of diazepam did not attenuate the anxiogenic-like effect of caerulein, but at more high doses of diazepam the coadministration depressed locomotor activity in mice. After subchronic diazepam treatment (2.5 mg/kg once a day, 10 days, i.p.) tolerance was developed toward the sedative effect of diazepam, and 72 h after withdrawal of the drug the animals showed increased anxiety in the plus-maze test. 30 min after the last injection procedure the anxiogenic-like effect of caerulein (500 ng/kg i.p.) on exploration was absent in both diazepam or vehicle groups. However, 72 h after the last pretreatment injection caerulein (500 ng/kg i.p.) reduced significantly the exploratory activity in control group, whereas it was inactive after diazepam withdrawal. The results obtained in this study support the hypothesis that endogenous CCK-8 an CCK-8 receptors are involved in the neurochemistry of anxiety and the anxiolytic action of benzodiazepine tranquillizers.
Harro
J
J
Laboratory of Psychopharmacology, Tartu University, Estonia, USSR.
Põld
M
M
Vasar
E
E
D000818:Animals; D001007:Anxiety / Q000139:chemically induced* / Q000523:psychology; D002108:Ceruletide / Q000494:pharmacology*; D003975:Diazepam / Q000494:pharmacology*; D004594:Electrophysiology; D005106:Exploratory Behavior / Q000187:drug effects; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D011377:Proglumide / Q000494:pharmacology; D011949:Receptors, Cholecystokinin / Q000187:drug effects / Q000502:physiology*; D012844:Sincalide / Q000378:metabolism*; D013375:Substance Withdrawal Syndrome / Q000523:psychology
D011949:Receptors, Cholecystokinin; D002108:Ceruletide; D011377:Proglumide; D012844:Sincalide; D003975:Diazepam