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Involvement of 5-HT2C and 5-HT1A receptors of the basolateral nucleus of the amygdala in the anxiolytic effect of chronic antidepressant treatment.
Neuropharmacology. 2014 Apr; 79:127-35.N

Abstract

Facilitation of serotonin 2C- and 1A-receptor (5-HT2C-R and 5-HT1A-R) mediated neurotransmission in the basolateral nucleus of the amygdala (BLA) has been associated with anxiogenic and anxiolytic effects, respectively. It has been also shown that stimulation of BLA 5-HT2C-Rs underlies the anxiogenic effect caused by acute systemic administration of the antidepressants imipramine or fluoxetine. Here we investigated whether chronic treatment with these two antidepressants, which causes anxiolytic effects, decreases the responsiveness of these receptors in the BLA. We also investigated whether the blockage of 5-HT1A-Rs in the same amygdala nucleus alters the anxiolytic effect of chronic imipramine treatment. The results showed that in male Wistar rats intra-BLA injection of the 5-HT2C-R agonist MK-212 facilitated inhibitory avoidance acquisition in the elevated T-maze and decreased the percentage of time spent by the animals in the lit compartment of the light-dark transition test, indicating an anxiogenic effect. Chronic (21 days) systemic treatment with imipramine (5 or 15 mg/kg) or fluoxetine (10 mg/kg) abolished these effects of MK-212. Acute administration of imipramine (5 mg/kg) failed to interfere with MK-212 effects in both tests. Intra-BLA injection of the 5-HT1A antagonist WAY-100635 blocked the anxiolytic, but not the panicolytic, effect of imipramine in the tests used. Our findings indicate that both a reduction in 5-HT2C-R- and a facilitation of 5-HT1A-R-mediated neurotransmission in the BLA are involved in the anxiolytic effect of antidepressant drugs.

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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, 14049-900 Ribeirão Preto, SP, Brazil.
Zangrossi H
Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, 14049-900 Ribeirão Preto, SP, Brazil. Electronic address: zangross@fmrp.usp.br.

MeSH

AmygdalaAnimalsAnti-Anxiety AgentsAntidepressive Agents, Second-GenerationAntidepressive Agents, TricyclicAnxietyAvoidance LearningExploratory BehaviorFluoxetineImipramineMaleMaze LearningPanicPiperazinesPyrazinesPyridinesRatsRats, WistarReceptor, Serotonin, 5-HT1AReceptor, Serotonin, 5-HT2CSerotonin 5-HT1 Receptor AntagonistsSerotonin 5-HT2 Receptor Agonists

Pub Type(s)

Journal Article

Language

eng

PubMed ID

24275045

Citation

Vicente, Maria Adrielle, and Helio Zangrossi. "Involvement of 5-HT2C and 5-HT1A Receptors of the Basolateral Nucleus of the Amygdala in the Anxiolytic Effect of Chronic Antidepressant Treatment." Neuropharmacology, vol. 79, 2014, pp. 127-35.
Vicente MA, Zangrossi H. Involvement of 5-HT2C and 5-HT1A receptors of the basolateral nucleus of the amygdala in the anxiolytic effect of chronic antidepressant treatment. Neuropharmacology. 2014;79:127-35.
Vicente, M. A., & Zangrossi, H. (2014). Involvement of 5-HT2C and 5-HT1A receptors of the basolateral nucleus of the amygdala in the anxiolytic effect of chronic antidepressant treatment. Neuropharmacology, 79, 127-35. https://doi.org/10.1016/j.neuropharm.2013.11.007
Vicente MA, Zangrossi H. Involvement of 5-HT2C and 5-HT1A Receptors of the Basolateral Nucleus of the Amygdala in the Anxiolytic Effect of Chronic Antidepressant Treatment. Neuropharmacology. 2014;79:127-35. PubMed PMID: 24275045.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Involvement of 5-HT2C and 5-HT1A receptors of the basolateral nucleus of the amygdala in the anxiolytic effect of chronic antidepressant treatment. AU - Vicente,Maria Adrielle, AU - Zangrossi,Helio,Jr Y1 - 2013/11/22/ PY - 2013/06/11/received PY - 2013/11/12/revised PY - 2013/11/13/accepted PY - 2013/11/27/entrez PY - 2013/11/28/pubmed PY - 2014/12/15/medline KW - 5-HT2C receptors KW - Antidepressants and basolateral amygdala KW - Anxiety KW - Serotonin SP - 127 EP - 35 JF - Neuropharmacology JO - Neuropharmacology VL - 79 N2 - Facilitation of serotonin 2C- and 1A-receptor (5-HT2C-R and 5-HT1A-R) mediated neurotransmission in the basolateral nucleus of the amygdala (BLA) has been associated with anxiogenic and anxiolytic effects, respectively. It has been also shown that stimulation of BLA 5-HT2C-Rs underlies the anxiogenic effect caused by acute systemic administration of the antidepressants imipramine or fluoxetine. Here we investigated whether chronic treatment with these two antidepressants, which causes anxiolytic effects, decreases the responsiveness of these receptors in the BLA. We also investigated whether the blockage of 5-HT1A-Rs in the same amygdala nucleus alters the anxiolytic effect of chronic imipramine treatment. The results showed that in male Wistar rats intra-BLA injection of the 5-HT2C-R agonist MK-212 facilitated inhibitory avoidance acquisition in the elevated T-maze and decreased the percentage of time spent by the animals in the lit compartment of the light-dark transition test, indicating an anxiogenic effect. Chronic (21 days) systemic treatment with imipramine (5 or 15 mg/kg) or fluoxetine (10 mg/kg) abolished these effects of MK-212. Acute administration of imipramine (5 mg/kg) failed to interfere with MK-212 effects in both tests. Intra-BLA injection of the 5-HT1A antagonist WAY-100635 blocked the anxiolytic, but not the panicolytic, effect of imipramine in the tests used. Our findings indicate that both a reduction in 5-HT2C-R- and a facilitation of 5-HT1A-R-mediated neurotransmission in the BLA are involved in the anxiolytic effect of antidepressant drugs. SN - 1873-7064 UR - https://www.unboundmedicine.com/medline/citation/24275045/Involvement_of_5_HT2C_and_5_HT1A_receptors_of_the_basolateral_nucleus_of_the_amygdala_in_the_anxiolytic_effect_of_chronic_antidepressant_treatment_ DB - PRIME DP - Unbound Medicine ER -