Role of neuropeptide Y Y₁ and Y₂ receptors on behavioral despair in a rat model of depression with co-morbid anxiety.

Accumulated evidence suggests that neuropeptide Y (NPY) is involved in emotional disorders by acting on Y(1) and Y(2) receptors. This hypothesis is based on animal studies carried out in naïve normal animals but not in animal models of depression, including the olfactory bulbectomized (OBX) rat. The OBX rat produces a wide array of symptoms that mimic several aspects of human depression and anxiety disorders. In the present study, we aimed to investigate the effects of sustained (2 weeks) intracerebroventricular administration of NPY Y(1) and Y(2) agonists and antagonists in a battery of behavioral tests including the open field, forced swim test (FST) and social interaction (SI) tests in OBX rats. The levels of Y(1) and Y(2) receptors in the hippocampus and basolateral amygdala (BLA) were also evaluated. Treatment with the Y(1)-like receptor agonist, [Leu(31)Pro(34)]PYY, decreased both depressive- and anxiogenic-like behaviors. The Y(2) receptor antagonist, BIIE0246, decreased the immobility time in the FST in OBX animals and increased active contacts in the SI test in sham rats. The Y(2) agonist, PYY3-36, increased the immobility time in the FST in OBX rats. Additionally, increased levels of Y(2) receptor binding were quantified in the dorsal hippocampus and BLA in OBX rats. Taken together, the autoradiographic results add further evidence that the NPYergic system is altered in disturbed emotional states. Moreover, we demonstrate a differential role for NPY Y(1) and Y(2) receptors in emotional processes under control and challenged conditions. This article is part of a Special Issue entitled 'Anxiety and Depression'.