Chronic psychosocial stress alters NPY system: different effects in rat and tree shrew.
The neuropeptide Y (NPY) system has been largely studied in relation to affective disorders, in particular for its role in the mechanisms regulating the pathophysiology of anxiety and depression and in the stress-related behaviours. Although NPY has been previously investigated in a variety of animal models of mood disorders, the receptor subtype mainly involved in the modulation of the stress response has not been identified. In the present study, the chronic psychosocial stress based on the resident-intruder protocol-an ethologically relevant paradigm known to induce behavioural and endocrine modifications which mimic depression-like symptoms-was used. Two different species were investigated: rat and tree shrew (Tupaia belangeri); the latter is regarded as an intermediate between insectivores and primates and it was chosen in this study for its pronounced territoriality. In these animals, the regulation of NPY and of Y(1), Y(2) and Y(5) receptors mRNA expression was evaluated after chronic stress and chronic antidepressant treatment by in situ hybridization in selected brain regions known to be involved in the pathophysiology of mood disorders. The animals were exposed to psychosocial stress for 35 days and concomitant daily fluoxetine treatment (10 mg/kg for rats and 15 mg/kg for tree shrews) after the first week of stress. The results confirmed a major role for hippocampal and hypothalamic NPY system in the pathophysiology of mood disorders. Although there were no evident differences between rat and tree shrew in the NPY system distribution, an opposite effect of chronic psychosocial stress was observed in the two species. Moreover, chronic antidepressant treatment was able to counteract the effects of stress and restored basal expression levels, suggesting the utility of these paradigms as preclinical models of stress-induced depression. Overall, although evident species differences were found in response to chronic psychosocial stress, the present study suggests a role for NPY receptors in the stress response and in the action of antidepressant drugs, providing further support for an involvement of this neuropeptidergic system in the pathophysiology of depression and anxiety.
Neurosciences Centre for Excellence in Drug Discovery, Mood & Anxiety Disorders DPU, GlaxoSmithKline Medicines Research Center, Verona, Italy. erika.2.zambello@gsk.com
E
E
Zambello
E
E
Fuchs
N
N
Abumaria
R
R
Rygula
E
E
Domenici
L
L
Caberlotto
D000704:Analysis of Variance; D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D005473:Fluoxetine / Q000494:pharmacology / Q000627:therapeutic use; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009478:Neuropeptide Y / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017476:Receptors, Neuropeptide Y / Q000235:genetics / Q000378:metabolism*; D013315:Stress, Psychological / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors; D014418:Tupaiidae
D018687:Antidepressive Agents, Second-Generation; D009478:Neuropeptide Y; D012333:RNA, Messenger; D017476:Receptors, Neuropeptide Y; D005473:Fluoxetine