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5-HT2C receptor regulation of defensive responses in the rat dorsal periaqueductal gray.
Neuropharmacology 2011 Feb-Mar; 60(2-3):216-22N

Abstract

Activation of 5-HT2C receptors in limbic structures such as the amygdala and hippocampus increases anxiety. Indirect evidence obtained with non-selective 5-HT2C-interacting drugs suggests that the same may occur in the dPAG, a brainstem region consistently implicated in the genesis/regulation of panic attacks. In this study we used more selective agonists and antagonists to unveil the role played by dPAG 5-HT2C receptors in the regulation of anxiety- and panic-related defensive behaviors. Our results showed that intra-dPAG microinjection of the endogenous agonist 5-HT (20 nmol) or the 5-HT2C receptor agonists MK-212 (1 and 10 nmol) and RO-600175 (40 nmol) significantly increased inhibitory avoidance acquisition in rats tested in the elevated T-maze, suggesting an anxiogenic effect. 5-HT, but not the two 5-HT2C receptor agonists, inhibited escape performance. In the elevated T-maze, inhibitory avoidance and escape responses have been related to generalized anxiety and panic attacks, respectively. The behavioral effects caused by 5-HT and MK-212 were fully blocked by previous local microinjection of the 5-HT2C receptor antagonist SB-242084. Intra-dPAG injection of MK-212 also failed to affect escape expression in another test relating this behavior to panic, the electrical stimulation of the dPAG. Overall, the results indicate that 5-HT2C receptors in the dPAG are preferentially involved in the regulation of defensive behaviors related to anxiety, but not panic. This finding extends to the dPAG the prominent role that has been attributed to 5-HT2C receptors in anxiety generation.

Authors+Show Affiliations

Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, 14049-900 Ribeirão Preto, Brazil. paulayamashita@usp.brNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

20850460

Citation

Yamashita, Paula Shimene de Melo, et al. "5-HT2C Receptor Regulation of Defensive Responses in the Rat Dorsal Periaqueductal Gray." Neuropharmacology, vol. 60, no. 2-3, 2011, pp. 216-22.
Yamashita PS, de Bortoli VC, Zangrossi H. 5-HT2C receptor regulation of defensive responses in the rat dorsal periaqueductal gray. Neuropharmacology. 2011;60(2-3):216-22.
Yamashita, P. S., de Bortoli, V. C., & Zangrossi, H. (2011). 5-HT2C receptor regulation of defensive responses in the rat dorsal periaqueductal gray. Neuropharmacology, 60(2-3), pp. 216-22. doi:10.1016/j.neuropharm.2010.09.001.
Yamashita PS, de Bortoli VC, Zangrossi H. 5-HT2C Receptor Regulation of Defensive Responses in the Rat Dorsal Periaqueductal Gray. Neuropharmacology. 2011;60(2-3):216-22. PubMed PMID: 20850460.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 5-HT2C receptor regulation of defensive responses in the rat dorsal periaqueductal gray. AU - Yamashita,Paula Shimene de Melo, AU - de Bortoli,Valquiria Camin, AU - Zangrossi,Helio,Jr Y1 - 2010/09/17/ PY - 2010/06/18/received PY - 2010/08/17/revised PY - 2010/09/03/accepted PY - 2010/9/21/entrez PY - 2010/9/21/pubmed PY - 2011/12/13/medline SP - 216 EP - 22 JF - Neuropharmacology JO - Neuropharmacology VL - 60 IS - 2-3 N2 - Activation of 5-HT2C receptors in limbic structures such as the amygdala and hippocampus increases anxiety. Indirect evidence obtained with non-selective 5-HT2C-interacting drugs suggests that the same may occur in the dPAG, a brainstem region consistently implicated in the genesis/regulation of panic attacks. In this study we used more selective agonists and antagonists to unveil the role played by dPAG 5-HT2C receptors in the regulation of anxiety- and panic-related defensive behaviors. Our results showed that intra-dPAG microinjection of the endogenous agonist 5-HT (20 nmol) or the 5-HT2C receptor agonists MK-212 (1 and 10 nmol) and RO-600175 (40 nmol) significantly increased inhibitory avoidance acquisition in rats tested in the elevated T-maze, suggesting an anxiogenic effect. 5-HT, but not the two 5-HT2C receptor agonists, inhibited escape performance. In the elevated T-maze, inhibitory avoidance and escape responses have been related to generalized anxiety and panic attacks, respectively. The behavioral effects caused by 5-HT and MK-212 were fully blocked by previous local microinjection of the 5-HT2C receptor antagonist SB-242084. Intra-dPAG injection of MK-212 also failed to affect escape expression in another test relating this behavior to panic, the electrical stimulation of the dPAG. Overall, the results indicate that 5-HT2C receptors in the dPAG are preferentially involved in the regulation of defensive behaviors related to anxiety, but not panic. This finding extends to the dPAG the prominent role that has been attributed to 5-HT2C receptors in anxiety generation. SN - 1873-7064 UR - https://www.unboundmedicine.com/medline/citation/20850460/5_HT2C_receptor_regulation_of_defensive_responses_in_the_rat_dorsal_periaqueductal_gray_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0028-3908(10)00222-4 DB - PRIME DP - Unbound Medicine ER -