EnglishIntroduction The present study was designed to assess the antidepressant effects of UFP-101, a selective nociceptin/orphanin FQ peptide (NOP) receptor antagonist, in a validated animal model of depression: the chronic mild stress (CMS). Materials and methods and Results UFP-101 (5, 10 and 20 nmol/rat; i.c.v., once a day for 21 days) dose- and time-dependently reinstated sucrose consumption in stressed animals without affecting the same parameter in non-stressed ones. In the forced swimming test, UFP-101 reduced immobility of stressed rats from day 8 of treatment. After a 3-week treatment, rats were killed for biochemical evaluations. UFP-101 abolished increase in serum corticosterone induced by CMS and reverted changes in central 5-HT/5-HIAA ratio. The behavioural and biochemical effects of UFP-101 mimicked those of imipramine, the reference antidepressant drug, administered at the dose of 15 mg/kg (i.p.). Co-administration of nociceptin/orphanin FQ (5 nmol/rat, from day 12 to 21) prevented the effects of UFP-101. Brain-derived neurotrophic factor mRNA and protein in hippocampus were not reduced by CMS nor did UFP-101 modify these parameters. Discussion and Conclusion This study demonstrated that chronic treatment with UFP-101 produces antidepressant-like effects in rats subjected to CMS supporting the proposal that NOP receptors represent a candidate target for the development of innovative antidepressant drugs.
| Data di pubblicazione: | 2009 |
| Titolo: | Chronic treatment with the selective NOP receptor antagonist [Nphe1,Arg14,Lys15]N/OFQ-NH2 (UFP-101) reverses the behavioural and biochemical effects of unpredictable chronic mild stress in rats |
| Autore/i: | Vitale G; Ruggieri V; Filaferro M; Frigeri C; Alboni S; Tascedda F; Brunello N; Guerrini R; Cifani C; Massi M |
| Autore/i UNIMORE: | |
| Rivista: | |
| Volume: | 207 (2) |
| Pagina iniziale: | 173 |
| Pagina finale: | 189 |
| Citazione: | Chronic treatment with the selective NOP receptor antagonist [Nphe1,Arg14,Lys15]N/OFQ-NH2 (UFP-101) reverses the behavioural and biochemical effects of unpredictable chronic mild stress in rats / Vitale G; Ruggieri V; Filaferro M; Frigeri C; Alboni S; Tascedda F; Brunello N; Guerrini R; Cifani C; Massi M. - In: PSYCHOPHARMACOLOGY. - ISSN 0033-3158. - STAMPA. - 207 (2)(2009), pp. 173-189. |
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