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Effects of fluoxetine and buspirone on the panicolytic-like response induced by the activation of 5-HT1A and 5-HT2A receptors in the rat dorsal periaqueductal gray.
Psychopharmacology (Berl). 2006 Jan; 183(4):422-8.P

Abstract

RATIONALE

Administration of 5-hydroxytryptamine (5-HT)1A and 5-HT2A receptor agonists into the dorsal periaqueductal gray (DPAG) inhibits escape, a defensive behavior associated with panic attacks. Long-term treatment with the antipanic compound imipramine enhances the DPAG 5-HT1A- and 5-HT2A-receptor-mediated inhibition of escape, implicating these receptors in the mode of action of panicolytic drugs.

OBJECTIVES

In the present study, we investigated whether the inhibitory effect on escape elicited by the intra-DPAG injection of 5-HT1A and 5-HT2A receptor agonists is also enhanced after treatment with fluoxetine, another widely used antipanic drug. The effects of fluoxetine were compared to those of buspirone, an anxiolytic drug without major effect on panic disorder.

METHODS

Male Wistar rats, subchronically (3-6 days) or chronically (21-24 days) treated with fluoxetine (10 mg/kg i.p.) or chronically treated with buspirone (0.3 mg/kg i.p.), were intra-DPAG injected with 5-HT (20 nmol), the 5-HT1A receptor agonist (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin hydrobromide (8-OH-DPAT; 8 nmol) or the preferential 5-HT2A receptor agonist (+/-)-1-(2,5-dimethoxy-4-iodophenyl) piperazine dihydrochloride (DOI; 16 nmol). The intensity of electrical current that applied to the DPAG-evoked escape behavior was measured before and after the microinjection of these agonists.

RESULTS

The electrical current necessary to produce escape was increased after the microinjection of the three 5-HT receptor agonists in all groups of animals tested. However, this panicolytic-like effect was significantly higher in animals receiving long-term treatment with fluoxetine.

CONCLUSIONS

The results suggest that facilitation of the 5-HT1A- and 5-HT2A-receptor-mediated inhibition of DPAG neuronal activity is implicated in the beneficial effect of antidepressants in panic disorder.

Authors+Show Affiliations

de Bortoli VC
Department of Pharmacology, School of Medicine, University of São Paulo, 14049-900, Ribeirão Preto, SP, Brazil.
Nogueira RL
No affiliation info available
Zangrossi H
No affiliation info available

MeSH

8-Hydroxy-2-(di-n-propylamino)tetralinAmphetaminesAnimalsAnti-Anxiety AgentsBuspironeFluoxetineMaleMicroinjectionsPeriaqueductal GrayRatsRats, WistarReceptor, Serotonin, 5-HT1AReceptor, Serotonin, 5-HT2ASerotoninSerotonin Receptor AgonistsSelective Serotonin Reuptake Inhibitors

Pub Type(s)

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

Language

eng

PubMed ID

16258751

Citation

de Bortoli, Valquíria Camin, et al. "Effects of Fluoxetine and Buspirone On the Panicolytic-like Response Induced By the Activation of 5-HT1A and 5-HT2A Receptors in the Rat Dorsal Periaqueductal Gray." Psychopharmacology, vol. 183, no. 4, 2006, pp. 422-8.
de Bortoli VC, Nogueira RL, Zangrossi H. Effects of fluoxetine and buspirone on the panicolytic-like response induced by the activation of 5-HT1A and 5-HT2A receptors in the rat dorsal periaqueductal gray. Psychopharmacology (Berl). 2006;183(4):422-8.
de Bortoli, V. C., Nogueira, R. L., & Zangrossi, H. (2006). Effects of fluoxetine and buspirone on the panicolytic-like response induced by the activation of 5-HT1A and 5-HT2A receptors in the rat dorsal periaqueductal gray. Psychopharmacology, 183(4), 422-8.
de Bortoli VC, Nogueira RL, Zangrossi H. Effects of Fluoxetine and Buspirone On the Panicolytic-like Response Induced By the Activation of 5-HT1A and 5-HT2A Receptors in the Rat Dorsal Periaqueductal Gray. Psychopharmacology (Berl). 2006;183(4):422-8. PubMed PMID: 16258751.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of fluoxetine and buspirone on the panicolytic-like response induced by the activation of 5-HT1A and 5-HT2A receptors in the rat dorsal periaqueductal gray. AU - de Bortoli,Valquíria Camin, AU - Nogueira,Regina Lúcia, AU - Zangrossi,Hélio,Jr Y1 - 2005/10/29/ PY - 2005/04/27/received PY - 2005/08/30/accepted PY - 2005/11/1/pubmed PY - 2006/2/1/medline PY - 2005/11/1/entrez SP - 422 EP - 8 JF - Psychopharmacology JO - Psychopharmacology (Berl) VL - 183 IS - 4 N2 - RATIONALE: Administration of 5-hydroxytryptamine (5-HT)1A and 5-HT2A receptor agonists into the dorsal periaqueductal gray (DPAG) inhibits escape, a defensive behavior associated with panic attacks. Long-term treatment with the antipanic compound imipramine enhances the DPAG 5-HT1A- and 5-HT2A-receptor-mediated inhibition of escape, implicating these receptors in the mode of action of panicolytic drugs. OBJECTIVES: In the present study, we investigated whether the inhibitory effect on escape elicited by the intra-DPAG injection of 5-HT1A and 5-HT2A receptor agonists is also enhanced after treatment with fluoxetine, another widely used antipanic drug. The effects of fluoxetine were compared to those of buspirone, an anxiolytic drug without major effect on panic disorder. METHODS: Male Wistar rats, subchronically (3-6 days) or chronically (21-24 days) treated with fluoxetine (10 mg/kg i.p.) or chronically treated with buspirone (0.3 mg/kg i.p.), were intra-DPAG injected with 5-HT (20 nmol), the 5-HT1A receptor agonist (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin hydrobromide (8-OH-DPAT; 8 nmol) or the preferential 5-HT2A receptor agonist (+/-)-1-(2,5-dimethoxy-4-iodophenyl) piperazine dihydrochloride (DOI; 16 nmol). The intensity of electrical current that applied to the DPAG-evoked escape behavior was measured before and after the microinjection of these agonists. RESULTS: The electrical current necessary to produce escape was increased after the microinjection of the three 5-HT receptor agonists in all groups of animals tested. However, this panicolytic-like effect was significantly higher in animals receiving long-term treatment with fluoxetine. CONCLUSIONS: The results suggest that facilitation of the 5-HT1A- and 5-HT2A-receptor-mediated inhibition of DPAG neuronal activity is implicated in the beneficial effect of antidepressants in panic disorder. SN - 0033-3158 UR - https://www.unboundmedicine.com/medline/citation/16258751/Effects_of_fluoxetine_and_buspirone_on_the_panicolytic_like_response_induced_by_the_activation_of_5_HT1A_and_5_HT2A_receptors_in_the_rat_dorsal_periaqueductal_gray_ DB - PRIME DP - Unbound Medicine ER -