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Genetic regulation of extracellular serotonin by 5-hydroxytryptamine(1A) and 5-hydroxytryptamine(1B) autoreceptors in different brain regions of the mouse.
J Pharmacol Exp Ther. 2001 Sep; 298(3):1083-91.JP

Abstract

The regulation of extracellular levels of 5-hydroxytryptamine (serotonin) (5-HT) in the striatum and ventral hippocampus was studied using in vivo microdialysis in awake, unrestrained wild-type 5-HT(1A) and 5-HT(1B) receptor knockout mice. Systemic administration of the selective serotonin reuptake inhibitor fluoxetine evoked a significant dose-dependent increase in extracellular 5-HT in both the striatum and hippocampus at both 2.5 mg/kg (i.p.) and 20 mg/kg (i.p.) in wild-type mice. In 5-HT(1A) receptor knockout mice, the response to 2.5 mg/kg fluoxetine was significantly augmented in the striatum but not the hippocampus, whereas the response to 20 mg/kg fluoxetine was significantly greater in both brain regions. In 5-HT(1B) receptor knockout mice, the increase of extracellular 5-HT was augmented in the hippocampus but not the striatum at both doses of fluoxetine. The response pattern to fluoxetine alone in 5-HT receptor mutant mice corresponded with the effects of fluoxetine given with either the 5-HT(1A) receptor antagonist WAY 100635 (0.1 mg/kg i.p.) or the 5-HT(1B/1D) receptor antagonist GR 127935 (0.056 mg/kg) in wild-type mice. These results indicate common topographical regulation of 5-HT release in different brain regions by genetic mutation and pharmacological challenges. The 5-HT(1A) autoreceptor plays a larger role in regulating 5-HT release in the striatum and possibly other brain regions innervated by the dorsal raphe nucleus, whereas the role of the 5-HT(1B) receptor is relatively greater in the hippocampus and possibly other brain regions innervated by the median raphe nucleus.

Authors+Show Affiliations

Department of Pharmacology and Psychiatry, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6140, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

11504805

Citation

Knobelman, D A., et al. "Genetic Regulation of Extracellular Serotonin By 5-hydroxytryptamine(1A) and 5-hydroxytryptamine(1B) Autoreceptors in Different Brain Regions of the Mouse." The Journal of Pharmacology and Experimental Therapeutics, vol. 298, no. 3, 2001, pp. 1083-91.
Knobelman DA, Hen R, Lucki I. Genetic regulation of extracellular serotonin by 5-hydroxytryptamine(1A) and 5-hydroxytryptamine(1B) autoreceptors in different brain regions of the mouse. J Pharmacol Exp Ther. 2001;298(3):1083-91.
Knobelman, D. A., Hen, R., & Lucki, I. (2001). Genetic regulation of extracellular serotonin by 5-hydroxytryptamine(1A) and 5-hydroxytryptamine(1B) autoreceptors in different brain regions of the mouse. The Journal of Pharmacology and Experimental Therapeutics, 298(3), 1083-91.
Knobelman DA, Hen R, Lucki I. Genetic Regulation of Extracellular Serotonin By 5-hydroxytryptamine(1A) and 5-hydroxytryptamine(1B) Autoreceptors in Different Brain Regions of the Mouse. J Pharmacol Exp Ther. 2001;298(3):1083-91. PubMed PMID: 11504805.
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TY - JOUR T1 - Genetic regulation of extracellular serotonin by 5-hydroxytryptamine(1A) and 5-hydroxytryptamine(1B) autoreceptors in different brain regions of the mouse. AU - Knobelman,D A, AU - Hen,R, AU - Lucki,I, PY - 2001/8/16/pubmed PY - 2001/9/14/medline PY - 2001/8/16/entrez SP - 1083 EP - 91 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 298 IS - 3 N2 - The regulation of extracellular levels of 5-hydroxytryptamine (serotonin) (5-HT) in the striatum and ventral hippocampus was studied using in vivo microdialysis in awake, unrestrained wild-type 5-HT(1A) and 5-HT(1B) receptor knockout mice. Systemic administration of the selective serotonin reuptake inhibitor fluoxetine evoked a significant dose-dependent increase in extracellular 5-HT in both the striatum and hippocampus at both 2.5 mg/kg (i.p.) and 20 mg/kg (i.p.) in wild-type mice. In 5-HT(1A) receptor knockout mice, the response to 2.5 mg/kg fluoxetine was significantly augmented in the striatum but not the hippocampus, whereas the response to 20 mg/kg fluoxetine was significantly greater in both brain regions. In 5-HT(1B) receptor knockout mice, the increase of extracellular 5-HT was augmented in the hippocampus but not the striatum at both doses of fluoxetine. The response pattern to fluoxetine alone in 5-HT receptor mutant mice corresponded with the effects of fluoxetine given with either the 5-HT(1A) receptor antagonist WAY 100635 (0.1 mg/kg i.p.) or the 5-HT(1B/1D) receptor antagonist GR 127935 (0.056 mg/kg) in wild-type mice. These results indicate common topographical regulation of 5-HT release in different brain regions by genetic mutation and pharmacological challenges. The 5-HT(1A) autoreceptor plays a larger role in regulating 5-HT release in the striatum and possibly other brain regions innervated by the dorsal raphe nucleus, whereas the role of the 5-HT(1B) receptor is relatively greater in the hippocampus and possibly other brain regions innervated by the median raphe nucleus. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/11504805/Genetic_regulation_of_extracellular_serotonin_by_5_hydroxytryptamine_1A__and_5_hydroxytryptamine_1B__autoreceptors_in_different_brain_regions_of_the_mouse_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=11504805 DB - PRIME DP - Unbound Medicine ER -