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Regional patterns of compensation following genetic deletion of either 5-hydroxytryptamine(1A) or 5-hydroxytryptamine(1B) receptor in the mouse.
J Pharmacol Exp Ther. 2001 Sep; 298(3):1092-100.JP

Abstract

Plasticity in serotonergic transmission in serotonin or 5-hydroxytryptamine (5-HT) receptor mutants was examined by measuring the regulation of extracellular 5-HT levels in the striatum and ventral hippocampus of 5-HT(1A) and 5-HT(1B) receptor knockout mice using in vivo microdialysis. The efficacy of genetic deletion was verified by showing blunted regulation of extracellular 5-HT with selective 5-HT receptor agonists. 5-HT(1A) receptor knockout mice failed to demonstrate reduction of extracellular 5-HT in response to systemic administration of the 5-HT(1A) receptor agonist R-8-hydroxydipropylaminotetralin (R-8-OH-DPAT) and 5-HT(1B) receptor knockout mice failed to demonstrate reduction of extracellular 5-HT in response to systemic administration of the 5-HT(1B) receptor agonist CP 94,253. Plasticity also developed to deletion of the complementary autoreceptor. 5-HT(1A) receptor knockout mice demonstrated a significantly greater response to CP 94,253 in the striatum, but not the ventral hippocampus, suggesting the development of enhanced sensitivity of striatal 5-HT(1B) receptors. In 5-HT(1B) receptor knockout mice, R-8-OH-DPAT evoked a significantly diminished response in the ventral hippocampus, but not the striatum, suggesting the potential desensitization of 5-HT(1A) receptors in the median raphe nucleus. The pattern of regional compensations between somatodendritic and terminal autoreceptors was confirmed by pharmacological challenges using the selective serotonin reuptake inhibitor fluoxetine combined with either a 5-HT(1A) (WAY 100635) or a 5-HT(1B/1D) (GR 127935) receptor antagonist. The regional pattern of compensation may be determined by the preferential role of 5-HT(1A) or 5-HT(1B) receptors in regulating 5-HT release. Taken together, these results demonstrate the development of regional plasticity between complementary somatodendritic and terminal autoreceptors after the genetic deletion of 5-HT(1A) or 5-HT(1B) receptors.

Authors+Show Affiliations

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

Pub Type(s)

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

Language

eng

PubMed ID

11504806

Citation

Knobelman, D A., et al. "Regional Patterns of Compensation Following Genetic Deletion of Either 5-hydroxytryptamine(1A) or 5-hydroxytryptamine(1B) Receptor in the Mouse." The Journal of Pharmacology and Experimental Therapeutics, vol. 298, no. 3, 2001, pp. 1092-100.
Knobelman DA, Hen R, Blendy JA, et al. Regional patterns of compensation following genetic deletion of either 5-hydroxytryptamine(1A) or 5-hydroxytryptamine(1B) receptor in the mouse. J Pharmacol Exp Ther. 2001;298(3):1092-100.
Knobelman, D. A., Hen, R., Blendy, J. A., & Lucki, I. (2001). Regional patterns of compensation following genetic deletion of either 5-hydroxytryptamine(1A) or 5-hydroxytryptamine(1B) receptor in the mouse. The Journal of Pharmacology and Experimental Therapeutics, 298(3), 1092-100.
Knobelman DA, et al. Regional Patterns of Compensation Following Genetic Deletion of Either 5-hydroxytryptamine(1A) or 5-hydroxytryptamine(1B) Receptor in the Mouse. J Pharmacol Exp Ther. 2001;298(3):1092-100. PubMed PMID: 11504806.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Regional patterns of compensation following genetic deletion of either 5-hydroxytryptamine(1A) or 5-hydroxytryptamine(1B) receptor in the mouse. AU - Knobelman,D A, AU - Hen,R, AU - Blendy,J A, AU - Lucki,I, PY - 2001/8/16/pubmed PY - 2001/9/14/medline PY - 2001/8/16/entrez SP - 1092 EP - 100 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 298 IS - 3 N2 - Plasticity in serotonergic transmission in serotonin or 5-hydroxytryptamine (5-HT) receptor mutants was examined by measuring the regulation of extracellular 5-HT levels in the striatum and ventral hippocampus of 5-HT(1A) and 5-HT(1B) receptor knockout mice using in vivo microdialysis. The efficacy of genetic deletion was verified by showing blunted regulation of extracellular 5-HT with selective 5-HT receptor agonists. 5-HT(1A) receptor knockout mice failed to demonstrate reduction of extracellular 5-HT in response to systemic administration of the 5-HT(1A) receptor agonist R-8-hydroxydipropylaminotetralin (R-8-OH-DPAT) and 5-HT(1B) receptor knockout mice failed to demonstrate reduction of extracellular 5-HT in response to systemic administration of the 5-HT(1B) receptor agonist CP 94,253. Plasticity also developed to deletion of the complementary autoreceptor. 5-HT(1A) receptor knockout mice demonstrated a significantly greater response to CP 94,253 in the striatum, but not the ventral hippocampus, suggesting the development of enhanced sensitivity of striatal 5-HT(1B) receptors. In 5-HT(1B) receptor knockout mice, R-8-OH-DPAT evoked a significantly diminished response in the ventral hippocampus, but not the striatum, suggesting the potential desensitization of 5-HT(1A) receptors in the median raphe nucleus. The pattern of regional compensations between somatodendritic and terminal autoreceptors was confirmed by pharmacological challenges using the selective serotonin reuptake inhibitor fluoxetine combined with either a 5-HT(1A) (WAY 100635) or a 5-HT(1B/1D) (GR 127935) receptor antagonist. The regional pattern of compensation may be determined by the preferential role of 5-HT(1A) or 5-HT(1B) receptors in regulating 5-HT release. Taken together, these results demonstrate the development of regional plasticity between complementary somatodendritic and terminal autoreceptors after the genetic deletion of 5-HT(1A) or 5-HT(1B) receptors. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/11504806/Regional_patterns_of_compensation_following_genetic_deletion_of_either_5_hydroxytryptamine_1A__or_5_hydroxytryptamine_1B__receptor_in_the_mouse_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=11504806 DB - PRIME DP - Unbound Medicine ER -