Effects of cholecystokinin and cholecystokinin antagonists on isolation-induced ultrasonic vocalizations in rat pups.
Date
2004
Authors
Mendella, Paul D.
Journal Title
Journal ISSN
Volume Title
Publisher
Dalhousie University
Abstract
Description
Rat pups emit ultrasonic vocalizations (UVs) when separated from the dam and littermates. Some investigators have suggested that isolation-induced UVs signify a behavioural manifestation of distress or anxiety. Many compounds that possess anxiolytic properties reduce isolation-induced UVs, whereas anxiogenic drugs increase UVs. The CCK tetrapeptide fragment (CCK-4) induces panic in humans, and individuals diagnosed with panic disorder exhibit a heightened sensitivity to the anxiogenic effects of CCK-4. However, the effects of CCK in traditional animal models of anxiety have been variable, and data examining the effects of CCK on isolation-induced UVs is limited. Previous studies have demonstrated an anxioselective effect for CCK-8s in 11-day-old rats (Weller & Blass, 1988), although negative results have been reported with younger pups (Rex, Barth, Voight, Domeney, & Fink, 1994; Weller & Dubson, 1998). CCK-4 has been shown to increase UV rates (Rex et al., 1994) in 5-day-old rats. The current series of experiments was designed to assess the effects of various CCK fragments and antagonists on isolation-induced UVs, motor activity, and body temperature in 12-day-old, Long Evans hooded rats. It was hypothesized that CCK-4 would increase, whereas CCK-8s would decrease, UV rates. In Experiments 1--4, subjects were treated with BOC-CCK-4 (which acts on CCK-2 receptors) or CCK-8s (which acts on CCK-1 and CCK-2 receptors), and UVs, motor activity, and body temperature were examined 15 or 30 minutes following drug pre-treatment. Contrary to expectations, BOC-CCK-4 failed to exert any significant effects on UVs (Experiments 1 and 2), and CCK-8s, administered 15 minutes prior to testing, was also without effect on call rates (Experiment 3). In Experiment 4, CCK-8s (30 minutes post-treatment) reduced UV rates at each of the doses tested (0.5, 1.0, 2.0 and 4.0 mug/kg). This effect on UVs was specific in that motor activity and body temperature were unaffected. In Experiments 5 and 6, pups were pre-treated with vehicle, devazepide (a CCK-1 receptor antagonist), or L-365,260 (a CCK-2 receptor antagonist), respectively, 45 minutes prior to testing. (Abstract shortened by UMI.)
Thesis (Ph.D.)--Dalhousie University (Canada), 2004.
Thesis (Ph.D.)--Dalhousie University (Canada), 2004.
Keywords
Biology, Neuroscience., Health Sciences, Pharmacology., Psychology, Physiological.