The CCK-system mediates adaptation to novelty-induced stress in the rat: a pharmacological evidence.
Brain cholecystokinin (CCK) and its receptor CCK(2) have been implicated in the etiology of anxiety. CCK(2) antagonists, however, fail to ameliorate anxiety in humans. In this study, a role for CCK in adaptation to stress is investigated by testing carry-over effects of Ly225.910, a potent CCK(2) antagonist, in a rat model of individual differences in novelty-induced emotionality. Novelty-seeking behavior in the rat is thought to model some aspects of sensation-seeking, a personality trait closely associated with risk activities including substance abuse. Animals were categorized as high-responders (HR) and low-responders (LR) based on the activity response to an inescapable novel environment. High-responders exhibit increased exploration and proactive behavior while low-responders are less exploratory and deemed to behave more anxiously. We analyzed the effects of the CCK(2) antagonist Ly225.910 (0.1 mg/kg or 0.5 mg/kg, i.p.) on the anxiety displayed by HR and LR rats in the light-dark (LD) box test (Day 1). Treatment and phenotype effects were not acutely evident. LD-experienced rats were then re-exposed to drug-free LD-box (Days 4 and 11) and elevated plus-maze (EPM) test (Day 14). Drug-naïve HR rats behaved less anxiously than drug-naïve LR rats while exploring the open arms. Previous exposure to the antagonist curtailed these differences. The emotional responses in drug-naïve HR and LR rats to the EPM test could reflect different degrees of adaptation to anxiety-like training. Long-term effects of Ly225.910 on EPM-induced risk assessment in HR and LR rats suggest that CCK-system may be involved in modulating preparedness to arousing environmental changes.
Ballaz
Santiago J
SJ
Molecular and Behavioral Neuroscience Institute, The University of Michigan, Ann Arbor, MI 48109-0720, USA. sballaz@umich.edu
Akil
Huda
H
Watson
Stanley J
SJ
D000222:Adaptation, Physiological / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D002766:Cholecystokinin / Q000502:physiology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D052999:Quinazolinones / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors / Q000502:physiology*; D013315:Stress, Psychological / Q000378:metabolism* / Q000503:physiopathology*
C435663:2-(2-(5-bromo-1H-indol-3-yl)ethyl)-3-(1-methylethoxyphenyl)-4-(3H)-quinazolinone; D052999:Quinazolinones; D011949:Receptors, Cholecystokinin; D002766:Cholecystokinin