Animal Models of Depressive Illness: The Importance of Chronic Drug Treatment

Abstract

A wide diversity of animal models has been used to examine antidepressant activity. These range from relatively simple models sensitive to acute treatment, to highly sophisticated models that reputedly model some aspect of depressive illness and which yield a positive response to prolonged, chronic, drug treatment. In recent years antidepressant drug research has focused on the search for antidepressant therapy that has a more rapid onset of action. To be relevant, therefore, animal models must measure the time course of drug action. This review examines the claims of animal models to be sensitive to chronic drug treatment and considers their relevance. First, the review addresses the criteria necessary to examine the validity of animal models of depressive illness. Second, those animal models sensitive to chronic antidepressant treatment are reviewed with respect to their validity as animal models of either depressive illness and/or antidepressant activity. In particular, the development and utility of two "ethologically-relevant" animal models, the resident-intruder and social hierarchy paradigms, are described in detail. These models of rodent social and agonistic behaviour demonstrate that acute and chronic treatment with antidepressant drugs (regardless of their acute pharmacological activity) induce diametrically opposite changes in rodent agonistic behaviour. It is argued that the common ability of chronic treatment to increase rodent aggression (which in turn results in increased hierarchical status in closed social groups) most likely reflects the increased assertiveness and associated externalization of emotions expressed during recovery from depressive illness. Finally, findings that relate observed behavioural changes to underlying neurochemical changes are briefly reviewed.

Effect of nicotine on serotonin (5-HT) levels in brain of depressed rats

“…18 Social isolation stress is a valuable stress paradigm for investigating the effects of chronic psychosocial stress on various pathophysiological alterations in animals. 19 Therefore, we conducted this study that compared the effects of imipramine, a tricyclic antidepressant and nicotine. Nicotine was administered by subcutaneous as well as inhalational route.…”

Innovative approaches for the development of antidepressant drugs: Current and future strategies

“…58 5-HT 2C receptor agonists are also effective in additional models of antidepressant action including the DRL-72 s (DRL ϭ differential reinforcement of low rate) model, the resident-intruder model, the olfactory bulbectomy model and the chronic mild stress model. 51,59,60 In both the chronic mild stress model and in the olfactory bulbectomy model, antidepressants typically require 2-3 weeks of administration to show effectiveness. 5-HT 2C receptor agonists are effective by day 3 in the chronic mild stress model and are effective following short-term treatment (Ͻ1 week) in the olfactory bulbectomy model, consistent with rapid onset antidepressant-like effects (Rosenzweig-Lipson, S., unpublished observation).…”

Neuroleptics and animal models: feasibility of oral treatment monitored by plasma levels and receptor occupancy assays

“…For example, the administration of drugs by various injection techniques are very accurate in determining the amount of drug delivered, but can produce a high rate of stress to the animals in multi-dosing experiments (Stahle and Ungerstedt 1986;Schmitt et al 1999;Schleimer et al 2005) and large differences in drug availability between injections (see Kapur et al 2003). Another widely used approach is the use of osmotic mini-pumps since this methodology reduces the stress associated with repeated injections and handling, which could alter the subject's behavioral profile (Mitchell and Redfern 2005). However, this later method could be difficult to use in large-scale experiments, as suggested by the study by Kapur et al (2003), and may be inappropriate for the delivery of some APDs like clozapine or quetiapine.…”