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Alprazolam potentiates the antiaversive effect induced by the activation of 5-HT(1A) and 5-HT (2A) receptors in the rat dorsal periaqueductal gray.
Psychopharmacology (Berl). 2008 Jun; 198(3):341-9.P

Abstract

RATIONALE

Serotonin in the dorsal periaqueductal gray (DPAG) through the activation of 5-HT(1A) and 5-HT(2A) receptors inhibits escape, a defensive behavior associated with panic attacks. Long-term treatment with antipanic drugs that nonselectively or selectively blocks the reuptake of serotonin (e.g., imipramine and fluoxetine, respectively) enhances the inhibitory effect on escape caused by intra-DPAG injection of 5-HT(1A) and 5-HT(2A) receptor agonists. It has been proposed that these compounds exert their effect on panic by facilitating 5-HT-mediated neurotransmission in the DPAG.

OBJECTIVES

The objective of this study was to investigate whether facilitation of 5-HT neurotransmission in the DPAG is also observed after treatment with alprazolam, a pharmacologically distinct antipanic drug that acts primarily as a high potency benzodiazepine receptor agonist.

MATERIALS AND METHODS

Male Wistar rats, subchronically (3-6 days) or chronically (14-17 days) treated with alprazolam (2 and 4 mg/kg, i.p.) were intra-DPAG injected with (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin hydrobromide (8-OH-DPAT), (+/-)-1-(2,5-dimethoxy-4-iodophenyl) piperazine dihydrochloride (DOI), and midazolam, respectively, 5-HT(1A), 5-HT(2A/2C), and benzodiazepine receptor agonists. The intensity of electrical current that needed to be applied to the DPAG to evoke escape behavior was measured before and after the microinjection of these agonists.

RESULTS

Intra-DPAG injection of the 5-HT agonists and midazolam increased the escape threshold in all groups of animals tested, indicating a panicolytic-like effect. The inhibitory effect of 8-OH-DPAT and DOI, but not midazolam, was significantly higher in animals receiving long-, but not short-term treatment with alprazolam.

CONCLUSIONS

Alprazolam as antidepressants compounds facilitates 5-HT(1A)- and 5-HT(2A)-receptor-mediated neurotransmission in the DPAG, implicating this effect in the mode of action of different classes of antipanic drugs.

Links

Publisher Full Text (DOI)

Authors+Show Affiliations

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

MeSH

8-Hydroxy-2-(di-n-propylamino)tetralinAlprazolamAmphetaminesAnimalsAnti-Anxiety AgentsDose-Response Relationship, DrugElectric StimulationMaleMicroinjectionsPeriaqueductal GrayRatsRats, WistarSerotonin 5-HT1 Receptor AgonistsSerotonin 5-HT2 Receptor AgonistsSerotonin Receptor AgonistsSynaptic Transmission

Pub Type(s)

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

Language

eng

PubMed ID

18446327

Citation

de Bortoli, Valquíria Camin, et al. "Alprazolam Potentiates the Antiaversive Effect Induced By the Activation of 5-HT(1A) and 5-HT (2A) Receptors in the Rat Dorsal Periaqueductal Gray." Psychopharmacology, vol. 198, no. 3, 2008, pp. 341-9.
de Bortoli VC, Nogueira RL, Zangrossi H. Alprazolam potentiates the antiaversive effect induced by the activation of 5-HT(1A) and 5-HT (2A) receptors in the rat dorsal periaqueductal gray. Psychopharmacology (Berl). 2008;198(3):341-9.
de Bortoli, V. C., Nogueira, R. L., & Zangrossi, H. (2008). Alprazolam potentiates the antiaversive effect induced by the activation of 5-HT(1A) and 5-HT (2A) receptors in the rat dorsal periaqueductal gray. Psychopharmacology, 198(3), 341-9. https://doi.org/10.1007/s00213-008-1134-7
de Bortoli VC, Nogueira RL, Zangrossi H. Alprazolam Potentiates the Antiaversive Effect Induced By the Activation of 5-HT(1A) and 5-HT (2A) Receptors in the Rat Dorsal Periaqueductal Gray. Psychopharmacology (Berl). 2008;198(3):341-9. PubMed PMID: 18446327.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Alprazolam potentiates the antiaversive effect induced by the activation of 5-HT(1A) and 5-HT (2A) receptors in the rat dorsal periaqueductal gray. AU - de Bortoli,Valquíria Camin, AU - Nogueira,Regina Lúcia, AU - Zangrossi,Hélio,Jr Y1 - 2008/04/30/ PY - 2007/10/08/received PY - 2008/03/01/accepted PY - 2008/5/1/pubmed PY - 2008/11/18/medline PY - 2008/5/1/entrez SP - 341 EP - 9 JF - Psychopharmacology JO - Psychopharmacology (Berl) VL - 198 IS - 3 N2 - RATIONALE: Serotonin in the dorsal periaqueductal gray (DPAG) through the activation of 5-HT(1A) and 5-HT(2A) receptors inhibits escape, a defensive behavior associated with panic attacks. Long-term treatment with antipanic drugs that nonselectively or selectively blocks the reuptake of serotonin (e.g., imipramine and fluoxetine, respectively) enhances the inhibitory effect on escape caused by intra-DPAG injection of 5-HT(1A) and 5-HT(2A) receptor agonists. It has been proposed that these compounds exert their effect on panic by facilitating 5-HT-mediated neurotransmission in the DPAG. OBJECTIVES: The objective of this study was to investigate whether facilitation of 5-HT neurotransmission in the DPAG is also observed after treatment with alprazolam, a pharmacologically distinct antipanic drug that acts primarily as a high potency benzodiazepine receptor agonist. MATERIALS AND METHODS: Male Wistar rats, subchronically (3-6 days) or chronically (14-17 days) treated with alprazolam (2 and 4 mg/kg, i.p.) were intra-DPAG injected with (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin hydrobromide (8-OH-DPAT), (+/-)-1-(2,5-dimethoxy-4-iodophenyl) piperazine dihydrochloride (DOI), and midazolam, respectively, 5-HT(1A), 5-HT(2A/2C), and benzodiazepine receptor agonists. The intensity of electrical current that needed to be applied to the DPAG to evoke escape behavior was measured before and after the microinjection of these agonists. RESULTS: Intra-DPAG injection of the 5-HT agonists and midazolam increased the escape threshold in all groups of animals tested, indicating a panicolytic-like effect. The inhibitory effect of 8-OH-DPAT and DOI, but not midazolam, was significantly higher in animals receiving long-, but not short-term treatment with alprazolam. CONCLUSIONS: Alprazolam as antidepressants compounds facilitates 5-HT(1A)- and 5-HT(2A)-receptor-mediated neurotransmission in the DPAG, implicating this effect in the mode of action of different classes of antipanic drugs. SN - 0033-3158 UR - https://www.unboundmedicine.com/medline/citation/18446327/Alprazolam_potentiates_the_antiaversive_effect_induced_by_the_activation_of_5_HT_1A__and_5_HT__2A__receptors_in_the_rat_dorsal_periaqueductal_gray_ DB - PRIME DP - Unbound Medicine ER -