Vasoactive intestinal peptide (VIP) is a neuropeptide, which is widely distributed in the central nervous system and peripheral tissues, acting both as a neurotransmitter and neuromodulator. Despite its extensive expression in the hippocampus, amygdala and other limbic system structures, the effects of VIP on anxiety and depression have not yet been fully investigated. The aim of the present study was to evaluate the involvement of VIP and VIP receptors in the mechanism of anxiety in rats with a model of depression (bilateral olfactory bulbectomy), using the elevated plus-maze test. VIP and a non-specific antagonist of VIP receptors (VIP6-28) were administered unilaterally into the hippocampal CA1 area of bulbectomized (OBX) rats. VIP (10 ng) showed a tendency for an anxiety-modulatory effect upon right side injection, by reducing significantly the closed arm time and increasing the open arm time. VIP (100 ng) injected unilaterally (left or right) into CA1 area induced an anxiolytic-like effect on the activity of OBX rats (increased the number of open arms entries, open arm time and the ratio open/total number of entries). VIP6-28 failed to antagonize the anxiety-related behavior of OBX rats in the plus maze. An unexpected finding in our study was that upon pretreatment with VIP6-28, VIP (10 ng), injected unilaterally (left or right) exerted an anti-anxiety like effect (increased the number of open arm entries, open arm time and the ratio open/total number of entries). Our data point to a possible involvement of hippocampal VIP-ergic neurons in modulating emotional processes or adaptive responses to stressful stimuli in a rat model of depression.
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