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Serotonin-2C receptors in the basolateral nucleus of the amygdala mediate the anxiogenic effect of acute imipramine and fluoxetine administration.
Int J Neuropsychopharmacol. 2012 Apr; 15(3):389-400.IJ

Abstract

A growing body of evidence indicates that facilitation of serotonin-2C receptor (5-HT2CR)-mediated neurotransmission in the basolateral nucleus of the amygdala (BLA) is involved in anxiety generation. We investigated here whether BLA 5-HT2CRs exert a differential role in the regulation of defensive behaviours related to generalized anxiety (inhibitory avoidance) and panic (escape) disorders. We also evaluated whether activation of BLA 5-HT2CRs accounts for the anxiogenic effect caused by acute systemic administration of the antidepressants imipramine and fluoxetine. Male Wistar rats were tested in the elevated T-maze after intra-BLA injection of the endogenous agonist 5-HT, the 5-HT2CR agonist MK-212 or the 5-HT2CR antagonist SB-242084. This test allows the measurement of inhibitory avoidance acquisition and escape expression. We also investigated whether intra-BLA administration of SB-242084 interferes with the acute anxiogenic effect caused by imipramine and fluoxetine in the Vogel conflict test, and imipramine in the elevated T-maze. While intra-BLA administration of 5-HT and MK-212 facilitated inhibitory avoidance acquisition, suggesting an anxiogenic effect, SB-242084 had the opposite effect. None of these drugs affected escape performance. Intra-BLA injection of a sub-effective dose of SB-242084 fully blocked the anxiogenic effect caused either by the local microinjection of 5-HT or the systemic administration of imipramine and fluoxetine. Our findings indicate that 5-HT2CRs in BLA are selectively involved in the regulation of defensive behaviours associated with generalized anxiety, but not panic. The results also provide the first direct evidence that activation of BLA 5-HT2CRs accounts for the short-term aversive effect of antidepressants.

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Publisher Full Text (DOI)

Authors+Show Affiliations

Vicente MA
Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
Zangrossi H
Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.

MeSH

AminopyridinesAnimalsAnti-Anxiety AgentsAntidepressive Agents, Second-GenerationAntidepressive Agents, TricyclicAnxiety DisordersAvoidance LearningBasolateral Nuclear ComplexExploratory BehaviorFluoxetineImipramineIndolesMaleMaze LearningNeuropsychological TestsPyrazinesRats, WistarReceptor, Serotonin, 5-HT2CSerotoninSerotonin 5-HT2 Receptor AgonistsSerotonin 5-HT2 Receptor Antagonists

Pub Type(s)

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

Language

eng

PubMed ID

21733232

Citation

Vicente, Maria Adrielle, and Helio Zangrossi. "Serotonin-2C Receptors in the Basolateral Nucleus of the Amygdala Mediate the Anxiogenic Effect of Acute Imipramine and Fluoxetine Administration." The International Journal of Neuropsychopharmacology, vol. 15, no. 3, 2012, pp. 389-400.
Vicente MA, Zangrossi H. Serotonin-2C receptors in the basolateral nucleus of the amygdala mediate the anxiogenic effect of acute imipramine and fluoxetine administration. Int J Neuropsychopharmacol. 2012;15(3):389-400.
Vicente, M. A., & Zangrossi, H. (2012). Serotonin-2C receptors in the basolateral nucleus of the amygdala mediate the anxiogenic effect of acute imipramine and fluoxetine administration. The International Journal of Neuropsychopharmacology, 15(3), 389-400. https://doi.org/10.1017/S1461145711000873
Vicente MA, Zangrossi H. Serotonin-2C Receptors in the Basolateral Nucleus of the Amygdala Mediate the Anxiogenic Effect of Acute Imipramine and Fluoxetine Administration. Int J Neuropsychopharmacol. 2012;15(3):389-400. PubMed PMID: 21733232.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Serotonin-2C receptors in the basolateral nucleus of the amygdala mediate the anxiogenic effect of acute imipramine and fluoxetine administration. AU - Vicente,Maria Adrielle, AU - Zangrossi,Helio, Y1 - 2011/06/14/ PY - 2011/7/8/entrez PY - 2011/7/8/pubmed PY - 2015/1/23/medline SP - 389 EP - 400 JF - The international journal of neuropsychopharmacology JO - Int J Neuropsychopharmacol VL - 15 IS - 3 N2 - A growing body of evidence indicates that facilitation of serotonin-2C receptor (5-HT2CR)-mediated neurotransmission in the basolateral nucleus of the amygdala (BLA) is involved in anxiety generation. We investigated here whether BLA 5-HT2CRs exert a differential role in the regulation of defensive behaviours related to generalized anxiety (inhibitory avoidance) and panic (escape) disorders. We also evaluated whether activation of BLA 5-HT2CRs accounts for the anxiogenic effect caused by acute systemic administration of the antidepressants imipramine and fluoxetine. Male Wistar rats were tested in the elevated T-maze after intra-BLA injection of the endogenous agonist 5-HT, the 5-HT2CR agonist MK-212 or the 5-HT2CR antagonist SB-242084. This test allows the measurement of inhibitory avoidance acquisition and escape expression. We also investigated whether intra-BLA administration of SB-242084 interferes with the acute anxiogenic effect caused by imipramine and fluoxetine in the Vogel conflict test, and imipramine in the elevated T-maze. While intra-BLA administration of 5-HT and MK-212 facilitated inhibitory avoidance acquisition, suggesting an anxiogenic effect, SB-242084 had the opposite effect. None of these drugs affected escape performance. Intra-BLA injection of a sub-effective dose of SB-242084 fully blocked the anxiogenic effect caused either by the local microinjection of 5-HT or the systemic administration of imipramine and fluoxetine. Our findings indicate that 5-HT2CRs in BLA are selectively involved in the regulation of defensive behaviours associated with generalized anxiety, but not panic. The results also provide the first direct evidence that activation of BLA 5-HT2CRs accounts for the short-term aversive effect of antidepressants. SN - 1469-5111 UR - https://www.unboundmedicine.com/medline/citation/21733232/Serotonin_2C_receptors_in_the_basolateral_nucleus_of_the_amygdala_mediate_the_anxiogenic_effect_of_acute_imipramine_and_fluoxetine_administration_ DB - PRIME DP - Unbound Medicine ER -