Rat Hippocampus Of Npy, 5-the Ht Pam And Chronic Unpredictable Stress Depression Of The Relationship

Accumulated evidence indicates a role of the hippocampal 5-hydroxy-tryptamine (5-HT) neuropeptide Y (NPY) in the response to stress and modulation of depression. Peptidylglycineα-amidating monooxygenase (PAM) is a rate-limiting enzyme essential for the production of multiple bioactive neuropeptides, including NPY. But it is unclear whether and how the hippocampal 5-HT and NPY systems make contributions to chronic unpredicted mild stress (CUMS)-induced depression, an animal model of depression that closely mimics human depression. It is also unclear whether PAM has the relationship with CUMS induced depression. Here we observed that rats receiving a variety of chronic unpredictable mild stressors for 3 weeks showed a variety of behavioral measures of depression, including a significant reduction in body weight, sucrose preference, and locomotion, rearing and grooming in open field test , and a significant increase in immobility time in forced swimming test. So, our current protocol of a 3-week CUMS is able to induce a reliable rat model of depression with anhedonia, loss of interests, lost weight, psychomotor retardation and behavioral despair. We also observed the expression of NPY, 5-HT and PAM- immunopositive neurons in the dental gyrus (DG) of hippocampus in these groups ,which indicates that the depression induced by CUMS maybe is related with the decreased expression of hippocampal NPYor5-HT or maybe is related with the reduced amidated NPY induced by reduced PAM. While repeated injections of 5-HT or NPY into one side of the dorsal hippocampus can suppress or block CUMS-induced anhedonia, loss of interests, psychomotor retardation and behavioral despair. The beneficial effects of NPY and 5-HT on behavioral measures of depression were suppressed by pretreatment with the monoamine receptor antagonist Spiperone and the NPY Y1 receptor antagonist GR231118, respectively. These data suggest, reduced 5-HT and NPY neurotransmission in the hippocampus may make significant contributions to CUMS-induced depression via the interaction of hippocampal 5-HT and NPY systems. The decreased expression of PAM maybe is a main reason for depression.