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In vivo/ex vivo and behavioural study on central effects of 5-HT1B/1D and 5-HT1A antagonists in guinea pigs.
Pharmacol Biochem Behav. 2008 Jan; 88(3):196-204.PB

Abstract

Serotonin 5-HT1A and 5-HT1B/1D receptors control serotonin (5-HT) release and are targets for the pharmacological treatment of psychiatric disorders. We investigated effects of the 5-HT1B/1D antagonist GR127935, the 5-HT1A antagonist WAY 100635 and a combination of both in guinea pigs on the behaviour in the forced swimming test and on extracellular 5-HT in the hippocampus and the prefrontal cortex using in vivo microdialysis. Tissue content of 5-HT, 5-HIAA and 5-HT turnover (ratio 5-HIAA/5-HT) were determined in a sample containing i) the median and dorsal raphe nuclei, ii) the frontal cortex, or iii) the ventral hippocampus ex vivo. BEHAVIOUR: Administration of WAY 100635 (0.3-3.0 mg/kg, i.p.) or GR127935 (1.0-10.0 mg/kg, i.p.) or the combination of both delayed immobility in the forced swim test. MICRODIALYSIS: Systemic administration of WAY 100635 (1 mg/kg i.p.), perfusion with GR127935 (10 microM perfused into the frontal cortex) in the medial prefrontal cortex or the combination of both treatments had no significant effect on extracellular 5-HT. 5-HT TISSUE CONTENT AND 5-HT TURNOVER IN THE TISSUE: Compared to controls, WAY 100635, GR127935 and the combination thereof, decreased cortical 5-HT (-30%), increased 5-HIAA and consequently 5-HT turnover in the cortex threefold and the raphe nuclei twofold. WAY 100635 decreased 5-HT in the hippocampus (-40%), too. WAY 100635 and GR127935 and their combination increased hippocampal 5-HIAA and 5-HT turnover twofold, compared to controls. The results suggest that both 5-HT1 antagonists have subtle effects on 5-HT function under resting conditions; combined treatment has no superior effects compared to solitary treatment.

Authors+Show Affiliations

Institute of Pharmacology and Toxicology, School of Veterinary Medicine, Freie Universität Berlin, Koserstr. 20, 14195 Berlin, Germany. rex.andre@vetmed.fu-berlin.de <rex.andre@vetmed.fu-berlin.de>No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

17888505

Citation

Rex, A, et al. "In Vivo/ex Vivo and Behavioural Study On Central Effects of 5-HT1B/1D and 5-HT1A Antagonists in Guinea Pigs." Pharmacology, Biochemistry, and Behavior, vol. 88, no. 3, 2008, pp. 196-204.
Rex A, Voigt JP, Wicke KM, et al. In vivo/ex vivo and behavioural study on central effects of 5-HT1B/1D and 5-HT1A antagonists in guinea pigs. Pharmacol Biochem Behav. 2008;88(3):196-204.
Rex, A., Voigt, J. P., Wicke, K. M., & Fink, H. (2008). In vivo/ex vivo and behavioural study on central effects of 5-HT1B/1D and 5-HT1A antagonists in guinea pigs. Pharmacology, Biochemistry, and Behavior, 88(3), 196-204.
Rex A, et al. In Vivo/ex Vivo and Behavioural Study On Central Effects of 5-HT1B/1D and 5-HT1A Antagonists in Guinea Pigs. Pharmacol Biochem Behav. 2008;88(3):196-204. PubMed PMID: 17888505.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - In vivo/ex vivo and behavioural study on central effects of 5-HT1B/1D and 5-HT1A antagonists in guinea pigs. AU - Rex,A, AU - Voigt,J P, AU - Wicke,K M, AU - Fink,H, Y1 - 2007/08/08/ PY - 2006/10/27/received PY - 2007/07/12/revised PY - 2007/07/24/accepted PY - 2007/9/25/pubmed PY - 2008/4/10/medline PY - 2007/9/25/entrez SP - 196 EP - 204 JF - Pharmacology, biochemistry, and behavior JO - Pharmacol Biochem Behav VL - 88 IS - 3 N2 - Serotonin 5-HT1A and 5-HT1B/1D receptors control serotonin (5-HT) release and are targets for the pharmacological treatment of psychiatric disorders. We investigated effects of the 5-HT1B/1D antagonist GR127935, the 5-HT1A antagonist WAY 100635 and a combination of both in guinea pigs on the behaviour in the forced swimming test and on extracellular 5-HT in the hippocampus and the prefrontal cortex using in vivo microdialysis. Tissue content of 5-HT, 5-HIAA and 5-HT turnover (ratio 5-HIAA/5-HT) were determined in a sample containing i) the median and dorsal raphe nuclei, ii) the frontal cortex, or iii) the ventral hippocampus ex vivo. BEHAVIOUR: Administration of WAY 100635 (0.3-3.0 mg/kg, i.p.) or GR127935 (1.0-10.0 mg/kg, i.p.) or the combination of both delayed immobility in the forced swim test. MICRODIALYSIS: Systemic administration of WAY 100635 (1 mg/kg i.p.), perfusion with GR127935 (10 microM perfused into the frontal cortex) in the medial prefrontal cortex or the combination of both treatments had no significant effect on extracellular 5-HT. 5-HT TISSUE CONTENT AND 5-HT TURNOVER IN THE TISSUE: Compared to controls, WAY 100635, GR127935 and the combination thereof, decreased cortical 5-HT (-30%), increased 5-HIAA and consequently 5-HT turnover in the cortex threefold and the raphe nuclei twofold. WAY 100635 decreased 5-HT in the hippocampus (-40%), too. WAY 100635 and GR127935 and their combination increased hippocampal 5-HIAA and 5-HT turnover twofold, compared to controls. The results suggest that both 5-HT1 antagonists have subtle effects on 5-HT function under resting conditions; combined treatment has no superior effects compared to solitary treatment. SN - 0091-3057 UR - https://www.unboundmedicine.com/medline/citation/17888505/In_vivo/ex_vivo_and_behavioural_study_on_central_effects_of_5_HT1B/1D_and_5_HT1A_antagonists_in_guinea_pigs_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0091-3057(07)00238-9 DB - PRIME DP - Unbound Medicine ER -