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

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.