Synergistic anticataleptic effect of imipramine and nicotine in a rotenone-induced rat model

Psychopharmacology (Berl). 2019 Nov;236(11):3125-3133. doi: 10.1007/s00213-019-05261-9. Epub 2019 May 8.

Abstract

Rationale: Some antidepressants have been previously found to produce anti-parkinsonian effect; nicotine was known to mitigate experimental neurotoxic lesions. The anticataleptic efficacy of antidepressant-nicotine co-administration is unstudied.

Objectives: This work aimed to evaluate anticataleptic action of imipramine-nicotine combination in rotenone model.

Methods: Catalepsy was measured by the bar test. Concentrations of tyrosine hydroxylase, dopamine, and DOPAC were determined in the substantia nigra and dorsal striatum using ELISA and HPLC techniques; additionally, dopamine/DOPAC ratio was calculated for both areas.

Results: Imipramine and nicotine alone were ineffective; however, co-administration of the drugs significantly (p < 0.01) inhibited rotenone-induced catalepsy and mitigated neurochemical changes in the nigrostriatal system. Anticataleptic effect of the combination exceeded that of levodopa, a standard drug for anti-parkinsonian treatment.

Conclusion: The combined use of imipramine and nicotine at relatively low doses inhibits neurotoxin-induced catalepsy and nigrostriatal neurochemical changes. The co-administration of these drugs might be a new approach to the treatment of extrapyramidal dysfunctions.

Keywords: Catalepsy; Dopamine; Imipramine; Nicotine; Rotenone; Synergy; Tyrosine hydroxylase.

MeSH terms

  • Adrenergic Uptake Inhibitors / administration & dosage
  • Animals
  • Antidepressive Agents / administration & dosage
  • Catalepsy / chemically induced*
  • Catalepsy / drug therapy*
  • Disease Models, Animal*
  • Dose-Response Relationship, Drug
  • Imipramine / administration & dosage*
  • Insecticides / toxicity
  • Male
  • Nicotine / administration & dosage*
  • Nicotinic Agonists / administration & dosage
  • Rats
  • Rats, Sprague-Dawley
  • Rotenone / toxicity*
  • Substantia Nigra / drug effects
  • Substantia Nigra / physiology

Substances

  • Adrenergic Uptake Inhibitors
  • Antidepressive Agents
  • Insecticides
  • Nicotinic Agonists
  • Rotenone
  • Nicotine
  • Imipramine