NPY intraperitoneal injections produce antidepressant-like effects and downregulate BDNF in the rat hypothalamus.
OBJECTIVE
Several studies have documented an involvement of Neuropeptide Y (NPY) in stress-related disorders. Stress-related disorders are also characterized by changes in brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), neurotrophins implicated in the survival and function of neurons. Thus the aim of this study was to investigate whether an NPY intraperitoneal treatment has antidepressant-like effects in rats subjected to a classical stress paradigm, the Forced Swim Test (FST), in association with changes in local brain neurotrophin production.


METHODS
Rats were intraperitoneally injected with either NPY (60 μg/kg) or a vehicle for three consecutive days between two FST sessions and then tested for time spent (or delay onset) in immobile posture. Moreover, we measured by enzyme-linked immunosorbent assay (ELISA) neurotrophin levels in the hypothalamus and corticosterone levels in plasma.


RESULTS
The data showed that NPY induced a significant delay in the onset and a significant reduction in the duration of the immobility posture in FST. We also found that NPY decreased BDNF levels in the hypothalamus and corticosterone levels in plasma.


CONCLUSIONS
Immobility posture in FST can be reduced by antidepressant drugs. Thus, our data show an antidepressant-like effect of NPY associated with changes in BDNF levels in the hypothalamus and reduced activity of hypothalamic-pituitary-adrenal (HPA) axis.


CONCLUSIONS
These findings, while confirming the involvement of the NPY system in stress-related disorders, suggest that a less invasive route of administration, such as an intraperitoneal injection, may be instrumental in coping with stressful events in animal models and perhaps in humans.
Department of Clinical and Behavioral Neurology, IRCCS Santa Lucia Foundation, Rome, Italy.
Francesca
F
Gelfo
Paola
P
Tirassa
Paola
P
De Bartolo
Nicoletta
N
Croce
Sergio
S
Bernardini
Carlo
C
Caltagirone
Laura
L
Petrosini
Francesco
F
Angelucci
D000704:Analysis of Variance; D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage*; D001835:Body Weight / Q000187:drug effects; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D003345:Corticosterone / Q000097:blood; D003863:Depression / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects*; D004435:Eating / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D007031:Hypothalamus / Q000378:metabolism*; D008297:Male; D020932:Nerve Growth Factor / Q000378:metabolism; D009478:Neuropeptide Y / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D013550:Swimming / Q000523:psychology; D013997:Time Factors
D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor; D009478:Neuropeptide Y; D020932:Nerve Growth Factor; D003345:Corticosterone