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Dorsal raphe nucleus regulation of a panic-like defensive behavior evoked by chemical stimulation of the rat dorsal periaqueductal gray matter.

Abstract

Electrical or chemical stimulation of the dorsal periaqueductal gray matter (DPAG) evokes escape, a defensive behavior that has been related to panic attacks. Injection of 5-HT(1A) or 5-HT(2A) receptor agonists into this midbrain area inhibits this response. It has been proposed that the impairment of 5-HT mechanisms controlling escape at the level of the DPAG may underlie the susceptibility to panic attacks that characterizes the panic disorder. In this study we evaluated the effects of the pharmacological manipulation of the dorsal raphe nucleus (DRN), which are the main source of 5-HT input to the DPAG, on the escape response evoked in rats by the intra-DPAG injection of the nitric oxide donor SIN-1. The results showed that DRN administration of the 5-HT(1A) receptor agonist 8-OH-DPAT which inhibits the activity of 5-HT neurons favored the expression of escape induced by SIN-1. Intra-DRN injection of the excitatory amino acid kainic acid or the 5-HT(1A) receptor antagonist WAY-100635 did not change escape expression. However, both compounds fully blocked the escape reaction generated by intra-DPAG injection of the excitatory amino acid d,l-homocysteic acid (DLH). Overall, the results indicate that 5-HT neurons in the DRN exert a bidirectional control upon escape behavior generated by the DPAG. Taking into account the effect of WAY-100635 on DLH-induced escape, they also strengthen the view that DRN 5-HT(1A) autoreceptors are under tonic inhibitory influence by 5-HT.

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  • Authors+Show Affiliations

    ,

    Department of Pharmacology, School of Medicine, University of São Paulo, Av. Bandeirantes 3900, Ribeirão Preto, CEP, Brazil.

    , ,

    Source

    Behavioural brain research 213:2 2010 Dec 01 pg 195-200

    MeSH

    8-Hydroxy-2-(di-n-propylamino)tetralin
    Animals
    Disease Models, Animal
    Escape Reaction
    Homocysteine
    Kainic Acid
    Male
    Molsidomine
    Panic Disorder
    Periaqueductal Gray
    Piperazines
    Pyridines
    Raphe Nuclei
    Rats
    Rats, Wistar
    Serotonin 5-HT1 Receptor Agonists
    Serotonin 5-HT1 Receptor Antagonists

    Pub Type(s)

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

    Language

    eng

    PubMed ID

    20451559

    Citation

    Miguel, Tatiana Longo Borges, et al. "Dorsal Raphe Nucleus Regulation of a Panic-like Defensive Behavior Evoked By Chemical Stimulation of the Rat Dorsal Periaqueductal Gray Matter." Behavioural Brain Research, vol. 213, no. 2, 2010, pp. 195-200.
    Miguel TL, Pobbe RL, Spiacci Junior A, et al. Dorsal raphe nucleus regulation of a panic-like defensive behavior evoked by chemical stimulation of the rat dorsal periaqueductal gray matter. Behav Brain Res. 2010;213(2):195-200.
    Miguel, T. L., Pobbe, R. L., Spiacci Junior, A., & Zangrossi Junior, H. (2010). Dorsal raphe nucleus regulation of a panic-like defensive behavior evoked by chemical stimulation of the rat dorsal periaqueductal gray matter. Behavioural Brain Research, 213(2), pp. 195-200. doi:10.1016/j.bbr.2010.04.055.
    Miguel TL, et al. Dorsal Raphe Nucleus Regulation of a Panic-like Defensive Behavior Evoked By Chemical Stimulation of the Rat Dorsal Periaqueductal Gray Matter. Behav Brain Res. 2010 Dec 1;213(2):195-200. PubMed PMID: 20451559.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Dorsal raphe nucleus regulation of a panic-like defensive behavior evoked by chemical stimulation of the rat dorsal periaqueductal gray matter. AU - Miguel,Tatiana Longo Borges, AU - Pobbe,Roger Luis Henschel, AU - Spiacci Junior,Ailton, AU - Zangrossi Junior,Hélio, Y1 - 2010/05/06/ PY - 2010/03/18/received PY - 2010/04/26/revised PY - 2010/04/29/accepted PY - 2010/5/11/entrez PY - 2010/5/11/pubmed PY - 2010/10/20/medline SP - 195 EP - 200 JF - Behavioural brain research JO - Behav. Brain Res. VL - 213 IS - 2 N2 - Electrical or chemical stimulation of the dorsal periaqueductal gray matter (DPAG) evokes escape, a defensive behavior that has been related to panic attacks. Injection of 5-HT(1A) or 5-HT(2A) receptor agonists into this midbrain area inhibits this response. It has been proposed that the impairment of 5-HT mechanisms controlling escape at the level of the DPAG may underlie the susceptibility to panic attacks that characterizes the panic disorder. In this study we evaluated the effects of the pharmacological manipulation of the dorsal raphe nucleus (DRN), which are the main source of 5-HT input to the DPAG, on the escape response evoked in rats by the intra-DPAG injection of the nitric oxide donor SIN-1. The results showed that DRN administration of the 5-HT(1A) receptor agonist 8-OH-DPAT which inhibits the activity of 5-HT neurons favored the expression of escape induced by SIN-1. Intra-DRN injection of the excitatory amino acid kainic acid or the 5-HT(1A) receptor antagonist WAY-100635 did not change escape expression. However, both compounds fully blocked the escape reaction generated by intra-DPAG injection of the excitatory amino acid d,l-homocysteic acid (DLH). Overall, the results indicate that 5-HT neurons in the DRN exert a bidirectional control upon escape behavior generated by the DPAG. Taking into account the effect of WAY-100635 on DLH-induced escape, they also strengthen the view that DRN 5-HT(1A) autoreceptors are under tonic inhibitory influence by 5-HT. SN - 1872-7549 UR - https://www.unboundmedicine.com/medline/citation/20451559/Dorsal_raphe_nucleus_regulation_of_a_panic_like_defensive_behavior_evoked_by_chemical_stimulation_of_the_rat_dorsal_periaqueductal_gray_matter_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0166-4328(10)00336-0 DB - PRIME DP - Unbound Medicine ER -