Serotonin-1A receptors in the dorsal periaqueductal gray matter mediate the panicolytic-like effect of pindolol and paroxetine combination in the elevated T-maze

Neurosci Lett. 2011 May 9;495(1):63-6. doi: 10.1016/j.neulet.2011.03.040. Epub 2011 Mar 21.

Abstract

The β-adrenergic blocker and 5-HT(1A) receptor antagonist pindolol has been combined with selective serotonin reuptake inhibitors (SSRIs) in patients with depressive and anxiety disorders to shorten the onset of the clinical action and/or increase the proportion of responders. The results of a previous study have shown that pindolol potentiates the panicolytic effect of paroxetine in rats submitted to the elevated T-maze (ETM). Since reported evidence has implicated the 5-HT(1A) receptors of the dorsal periaqueductal gray matter (DPAG) in the panicolytic effect of antidepressants, rats treated with pindolol (5.0mg/kg, i.p.) and paroxetine (1.5mg/kg, i.p.) received a previous intra-DPAG injection of the selective 5-HT(1A) antagonist, WAY-100635 (0.4 μg) and were submitted to the ETM. Pretreatment with WAY-100635 reversed the increase in escape latency, a panicolytic effect, determined by the pindolol-paroxetine combination. These results implicate the 5-HT(1A) receptors of the DPAG in the panicolytic effect of the pindolol-paroxetine combination administered systemically. They also give further preclinical support for the use of this drug combination in the treatment of panic disorder.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Antagonists / pharmacology*
  • Animals
  • Drug Synergism
  • Escape Reaction / drug effects
  • Male
  • Maze Learning / drug effects*
  • Panic / drug effects*
  • Paroxetine / pharmacology*
  • Periaqueductal Gray / metabolism*
  • Pindolol / pharmacology*
  • Piperazines / pharmacology
  • Pyridines / pharmacology
  • Rats
  • Rats, Wistar
  • Reaction Time
  • Receptor, Serotonin, 5-HT1A / metabolism*
  • Selective Serotonin Reuptake Inhibitors / pharmacology*
  • Serotonin 5-HT1 Receptor Antagonists / pharmacology

Substances

  • Adrenergic beta-Antagonists
  • Piperazines
  • Pyridines
  • Serotonin 5-HT1 Receptor Antagonists
  • Serotonin Uptake Inhibitors
  • Receptor, Serotonin, 5-HT1A
  • Paroxetine
  • N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide
  • Pindolol