Effects of Interferon-α on Depressive-Like Behavior and Brain Neurochemistry in Rats Housed in Standard and Overcrowding Conditions

Immunotherapy with interferon-alpha (IFN-alpha) is frequently associated with neuropsychiatric consequences, including depression. Mechanisms underlying adverse effects of IFN-alpha are not fully understood. This study was aimed to determine whether intranasal administration of IFN-alpha can provoke depression-like behavior in rats and whether overcrowding stress can interfere or amplify the effects of IFN-alpha. To achieve this aim, effects of human IFN-alpha in low (50 IU/kg) and medium (8000 IU/kg) doses on the forced swimming test behavior and monoamines and their metabolite content in the brain structures of Wistar rats housed in standard and overcrowding conditions were investigated. Depressive-like behavior (increased immobility) was observed in rats housed in standard conditions after treatment with both doses of human IFN-alpha, as well as in vehicle-treated rats housed in stressful, overcrowding conditions. In standard conditions, a low dose of IFN- a produced a subtle alteration in the metabolism of dopamine only in one of the brain structures analyzed (nucleus accumbens). The medium dose of IFN-alpha induced more drastic neurochemical alterations in a larger number of brain structures. Overcrowding led to some changes in monoamine and their metabolite levels similar to those observed after IFN-alpha treatment with the medium dose in the standard housing conditions. In the overcrowded conditions, in contrast to the standard ones, IFN-alpha treatment in both doses reduced depression-like behavior and normalized neurochemical alterations induced by overcrowding. The results suggest that the effect of IFN-alpha on depression-like behavior and brain neurochemistry depends on the ongoing emotional status of animals: whether they are in stressful (overcrowded) or non-stressful (normal) conditions.