Pindolol potentiates the panicolytic effect of paroxetine in the elevated T-maze

LIFE SCIENCES

卷:87

Article

Sela, Vania R.¹  Roncon, Camila M.¹  Zangrossi, Helio, Jr.²  Graeff, Frederico G.³  Audi, Elisabeth A.¹ 

[1] Univ Estadual Maringa, Dept Pharm & Pharmacol, BR-87020900 Maringa, Parana, Brazil

[2] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Pharmacol, BR-14049 Ribeirao Preto, SP, Brazil

[3] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Neurosci & Behav Sci, BR-14049 Ribeirao Preto, SP, Brazil

关键词: beta-blocker;    Antidepressant;    Animal model;    Anxiety;    Panic;   

DOI  :  10.1016/j.lfs.2010.08.009

来源: Elsevier

【 摘 要 】

Aims: The beta-adrenergic and 5-HT1A receptor antagonist pindolol has been used in combination with antidepressant drugs, to shorten the time of onset of clinical efficacy and/or increase the proportion of responders in depressive and anxiety disorders. The aim of this study was to examine the interaction between pindolol and the selective serotonin reuptake inhibitor (SSRI), paroxetine in rats submitted to the elevated T-maze (ETM). Main methods: For assessing the drug combination effect, rats were administered with pindolol before paroxetine, using oral or intraperitoneal (i.p.) routes of acute administration, and were submitted to the ETM model. Key findings: The highest dose of pindolol used (15.0 mg/kg, i.p.) increased both inhibitory avoidance and escape latencies in the ETM, probably due to nonspecific motor deficit, since locomotion in a circular arena was also significantly decreased. The highest dose of paroxetine (3.0 mg/kg, i.p.) selectively impaired escape, considered a panicolytic effect. Combination of pindolol (5.0 mg/kg, i.p.) with an ineffective dose of paroxetine (1.5 mg/kg, i.p.) impaired escape, indicating a potentiation of the panicolytic effect of paroxetine. By the oral route, neither paroxetine (3.0 mg/kg) nor pindolol (5.0 mg/kg) alone were effective, but the combination treatment had a marked panicolytic effect, again indicating drug potentiation. Significance: The present results show that the combination of the ineffective doses of pindolol and paroxetine significantly increased escape latency, indicating a selective panicolytic effect. These findings give preclinical support for the use of this drug combination in the treatment of panic disorder (PD). (C) 2010 Elsevier Inc. All rights reserved.

【 授权许可】

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