Tags

Type your tag names separated by a space and hit enter

A role for serotonin in the antidepressant activity of NG-Nitro-L-arginine, in the rat forced swimming test.
Pharmacol Biochem Behav. 2010 Feb; 94(4):524-33.PB

Abstract

The present study determined regional serotonin (5-HT) synthesis and metabolism changes associated with the nitric oxide synthase (NOS) inhibitor N(G)-nitro-L-arginine (L-NA) and the influence of 5-HT receptor blockade in the antidepressant-like actions of L-NA in the forced swimming test (FST). Regional effects of L-NA (5,10 and 20mg/kg i.p.) on tryptophan hydroxylase (TPH) activity, the rate limiting enzyme for 5-HT synthesis, were determined by measuring accumulation of the transient intermediate 5-hydoxytryptophan (5-HTP) following in vivo administration of the amino acid decarboxylase inhibitor, NSD 1015 (100mg/kg). L-NA (5-20mg/kg) dose dependently increased 5-HTP accumulation, particularly in the amygdaloid cortex, following exposure to the FST. L-NA also provoked an increase in regional brain 5-HIAA concentrations and in the 5-HIAA:5-HT metabolism ratio. Co-treatment with NSD-1015 failed to consistently modify the antidepressant-like effects of L-NA in the FST. Sub-active doses of L-NA (1mg/kg) and the 5-HT re-uptake inhibitor fluoxetine (2.5mg/kg) acted synergistically to increase swimming in the test. Co-treatment with the non-selective 5-HT receptor antagonist metergoline (1, 2 and 4mg/kg), attenuated the L-NA (20mg/kg)-induced reduction in immobility and increase in swimming behaviours. Metergoline alone however provoked an increase in immobility and reduction in swimming behaviours in the test. A similar response was obtained following co-treatment with the preferential 5-HT(2A) receptor antagonist ketanserin (5mg/kg) and the 5-HT(2C) receptor antagonist RO-430440 (5mg/kg). Co-treatment with the 5-HT(1A) receptor antagonist WAY 100635 (0.3mg/kg) or the 5-HT(1B) receptor antagonist GR 127935 (4mg/kg) failed to influence the antidepressant-like activity of L-NA. Taken together these data provide further support for a role for 5-HT in the antidepressant-like properties of NOS inhibitors.

Authors+Show Affiliations

Neuropsychopharmacology Research Group, School of Pharmacy & Pharmaceutical Sciences and Trinity College Institute of Neuroscience, Trinity College, Dublin 2, Ireland.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19945477

Citation

Gigliucci, Valentina, et al. "A Role for Serotonin in the Antidepressant Activity of NG-Nitro-L-arginine, in the Rat Forced Swimming Test." Pharmacology, Biochemistry, and Behavior, vol. 94, no. 4, 2010, pp. 524-33.
Gigliucci V, Buckley KN, Nunan J, et al. A role for serotonin in the antidepressant activity of NG-Nitro-L-arginine, in the rat forced swimming test. Pharmacol Biochem Behav. 2010;94(4):524-33.
Gigliucci, V., Buckley, K. N., Nunan, J., O'Shea, K., & Harkin, A. (2010). A role for serotonin in the antidepressant activity of NG-Nitro-L-arginine, in the rat forced swimming test. Pharmacology, Biochemistry, and Behavior, 94(4), 524-33. https://doi.org/10.1016/j.pbb.2009.11.007
Gigliucci V, et al. A Role for Serotonin in the Antidepressant Activity of NG-Nitro-L-arginine, in the Rat Forced Swimming Test. Pharmacol Biochem Behav. 2010;94(4):524-33. PubMed PMID: 19945477.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A role for serotonin in the antidepressant activity of NG-Nitro-L-arginine, in the rat forced swimming test. AU - Gigliucci,Valentina, AU - Buckley,Kathleen Niamh, AU - Nunan,John, AU - O'Shea,Karen, AU - Harkin,Andrew, Y1 - 2009/11/26/ PY - 2009/05/23/received PY - 2009/10/08/revised PY - 2009/11/16/accepted PY - 2009/12/1/entrez PY - 2009/12/1/pubmed PY - 2010/4/30/medline SP - 524 EP - 33 JF - Pharmacology, biochemistry, and behavior JO - Pharmacol. Biochem. Behav. VL - 94 IS - 4 N2 - The present study determined regional serotonin (5-HT) synthesis and metabolism changes associated with the nitric oxide synthase (NOS) inhibitor N(G)-nitro-L-arginine (L-NA) and the influence of 5-HT receptor blockade in the antidepressant-like actions of L-NA in the forced swimming test (FST). Regional effects of L-NA (5,10 and 20mg/kg i.p.) on tryptophan hydroxylase (TPH) activity, the rate limiting enzyme for 5-HT synthesis, were determined by measuring accumulation of the transient intermediate 5-hydoxytryptophan (5-HTP) following in vivo administration of the amino acid decarboxylase inhibitor, NSD 1015 (100mg/kg). L-NA (5-20mg/kg) dose dependently increased 5-HTP accumulation, particularly in the amygdaloid cortex, following exposure to the FST. L-NA also provoked an increase in regional brain 5-HIAA concentrations and in the 5-HIAA:5-HT metabolism ratio. Co-treatment with NSD-1015 failed to consistently modify the antidepressant-like effects of L-NA in the FST. Sub-active doses of L-NA (1mg/kg) and the 5-HT re-uptake inhibitor fluoxetine (2.5mg/kg) acted synergistically to increase swimming in the test. Co-treatment with the non-selective 5-HT receptor antagonist metergoline (1, 2 and 4mg/kg), attenuated the L-NA (20mg/kg)-induced reduction in immobility and increase in swimming behaviours. Metergoline alone however provoked an increase in immobility and reduction in swimming behaviours in the test. A similar response was obtained following co-treatment with the preferential 5-HT(2A) receptor antagonist ketanserin (5mg/kg) and the 5-HT(2C) receptor antagonist RO-430440 (5mg/kg). Co-treatment with the 5-HT(1A) receptor antagonist WAY 100635 (0.3mg/kg) or the 5-HT(1B) receptor antagonist GR 127935 (4mg/kg) failed to influence the antidepressant-like activity of L-NA. Taken together these data provide further support for a role for 5-HT in the antidepressant-like properties of NOS inhibitors. SN - 1873-5177 UR - https://www.unboundmedicine.com/medline/citation/19945477/A_role_for_serotonin_in_the_antidepressant_activity_of_NG_Nitro_L_arginine_in_the_rat_forced_swimming_test_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0091-3057(09)00318-9 DB - PRIME DP - Unbound Medicine ER -