Role of serotonin (5-HT) in the antidepressant-like properties of neuropeptide Y (NPY) in the mouse forced swim test.
Neuropeptide Y (NPY) is thought to be implicated in depressive disorders. The mouse forced swim test (FST) is an animal model widely used as a predictor of the efficacy of antidepressant drugs. The present study was undertaken to explore the possible contribution of endogenous serotonin (5-HT) systems in the behavioral effects elicited by NPY in this model. The selective serotonin re-uptake inhibitor (SSRI), fluoxetine, was also tested for comparison. 5-HT was depleted prior to testing by the administration of the tryptophan hydroxylase inhibitor p-chlorophenylalanine (PCPA; 300 mg/kg, i.p., each day for 3 days; control mice received saline-vehicle over the same period). On the fourth day, mice received NPY (3 nmol, I.C.V.), fluoxetine (16 mg/kg, i.p.) or saline injections before testing in the FST. Both NPY and fluoxetine significantly reduced immobility time in saline-treated control animals. Pre-treatment with PCPA significantly blocked the effects of fluoxetine in the FST, confirming the role of endogenous 5-HT. Similarly, pre-treatment with PCPA also significantly attenuated the anti-immobility effects of NPY, thus suggesting a role for 5-HT in the effects of NPY in the FST. Quantitative receptor autoradiography revealed increases in specific [125I][Leu31, Pro34]PYY sites that were sensitive to BIBP3226 (Y1-like sites) in various brain regions. Specific [125I]GR231118 and [125I]PYY(3-36) binding levels were not changed following PCPA treatment, suggesting that depletion of endogenous 5-HT resulted in an apparent increase in the level of Y1 sites in their high-affinity state. Taken together, these results suggest a role for 5-HT-related systems in the antidepressant-like properties of NPY.
Redrobe
John P
JP
Douglas Hospital Resarch Centre, McGill University, Department of Psychiatry, 6875 Blvd. LaSalle, Montréal (Verdun), Que., Canada H4H 1R3.
Dumont
Yvan
Y
Fournier
Alain
A
Baker
Glen B
GB
Quirion
Rémi
R
D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage*; D004195:Disease Models, Animal; D010134:Fenclonine / Q000008:administration & dosage*; D005473:Fluoxetine / Q000008:administration & dosage / Q000037:antagonists & inhibitors; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D009478:Neuropeptide Y / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000502:physiology; D012701:Serotonin / Q000502:physiology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage; D013550:Swimming / Q000502:physiology
D000928:Antidepressive Agents; D010134:Fenclonine; D005473:Fluoxetine; D009478:Neuropeptide Y; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors