Pindolol potentiates the panicolytic effect of paroxetine in the elevated T-maze.
OBJECTIVE
the β-adrenergic and 5-HT(1A) 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).


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.


RESULTS
the highest dose of pindolol used (15.0mg/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 (3.0mg/kg, i.p.) selectively impaired escape, considered a panicolytic effect. Combination of pindolol (5.0mg/kg, i.p.) with an ineffective dose of paroxetine (1.5mg/kg, i.p.) impaired escape, indicating a potentiation of the panicolytic effect of paroxetine. By the oral route, neither paroxetine (3.0mg/kg) nor pindolol (5.0mg/kg) alone were effective, but the combination treatment had a marked panicolytic effect, again indicating drug potentiation.


CONCLUSIONS
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).
Sela
Vânia R
VR
Department of Pharmacy and Pharmacology, State University of Maringá, Maringá, Pr, Brazil.
Roncon
Camila M
CM
Zangrossi
Hélio
H
Graeff
Frederico G
FG
Audi
Elisabeth A
EA
D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage* / Q000627:therapeutic use; D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000008:administration & dosage* / Q000627:therapeutic use; D001008:Anxiety Disorders / Q000188:drug therapy*; D004338:Drug Combinations; D004347:Drug Interactions; D008297:Male; D016584:Panic Disorder / Q000188:drug therapy*; D017374:Paroxetine / Q000008:administration & dosage* / Q000627:therapeutic use; D010869:Pindolol / Q000008:administration & dosage* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use
D000319:Adrenergic beta-Antagonists; D018687:Antidepressive Agents, Second-Generation; D004338:Drug Combinations; D017374:Paroxetine; D010869:Pindolol; D017367:Selective Serotonin Reuptake Inhibitors