Antidepressant-like activity of liposomal formulation containing nimodipine treatment in the tail suspension test, forced swim test and MAOB activity in mice

Brain Res. 2016 Sep 1:1646:235-240. doi: 10.1016/j.brainres.2016.06.004. Epub 2016 Jun 4.

Abstract

Previous studies have shown that intracellular calcium ion dysfunction may be an etiological factor in affective illness. Nimodipine (NMD) is a Ca(2+) channel blocker that has been extensively investigated for therapy of central nervous system (CNS) disorders. In this work, we have evaluated the antidepressant-like activity of nimodipine encapsulated into liposomes (NMD-Lipo) in mice through tail suspension and forced swim assays, as well as MAOB activity. During the tail suspension test, the administration of NMD-Lipo at 0.1, 1 and 10mg/kg was able to promote a reduction in the immobility time of animals greater than the positive control (imipramine). In the forced swim test, the immobility time of mice treated with NMD-Lipo was reduced. This reduction was significantly greater than that found in the animals treated with imipramine and paroxetine. This may suggest that NMD-Lipo provides more antidepressant-like activity than in positive controls. The groups that received a combination of liposomal NMD and antidepressant drugs showed lower immobility time than the groups, which were treated only with imipramine or paroxetine. The mice treated with the combination of NMD-Lipo and reserpine presented an increase in the time of immobility compared with animals treated only with NMD-Lipo. There was a significant decrease in MAOB activity in animals treated with NMD-Lipo compared with untreated animals. The results of the tail suspension test, forced swim test and MAOB activity suggested that the antidepressant activity of NMD-Lipo may be related to an increase in the cerebral monoamine concentrations.

Keywords: Forced swim test; Liposomes; Mice; Monoamine oxidase; Nimodipine; Tail suspension test.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antidepressive Agents / administration & dosage*
  • Antidepressive Agents / pharmacology
  • Antidepressive Agents, Second-Generation / administration & dosage
  • Antidepressive Agents, Tricyclic / administration & dosage
  • Behavior, Animal / drug effects
  • Calcium Channel Blockers / administration & dosage*
  • Depressive Disorder / drug therapy*
  • Depressive Disorder / metabolism
  • Hindlimb Suspension
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Imipramine / administration & dosage
  • Liposomes / administration & dosage
  • Liposomes / pharmacology
  • Male
  • Mice
  • Monoamine Oxidase / metabolism
  • Nimodipine / administration & dosage*
  • Nimodipine / pharmacology
  • Paroxetine / administration & dosage

Substances

  • Antidepressive Agents
  • Antidepressive Agents, Second-Generation
  • Antidepressive Agents, Tricyclic
  • Calcium Channel Blockers
  • Liposomes
  • Paroxetine
  • Nimodipine
  • Monoamine Oxidase
  • Imipramine