Synergistic anticataleptic effect of imipramine and nicotine in a rotenone-induced rat model
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.
This work aimed to evaluate anticataleptic action of imipramine-nicotine combination in rotenone model.
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.
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.
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.
KeywordsImipramine Nicotine Catalepsy Rotenone Dopamine Tyrosine hydroxylase Synergy
This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. I.D.I. is indebted to his long-standing mentors, Prof. Igor Efimovich Kovalev and Prof. Lev Aramovich Piruzyan. The study was supported by the Ministry of Science and Higher Education of the Russian Federation (project АААА-А18-118012390247-0).
Compliance with ethical standards
All experimental animal procedures were conducted according to the European Communities Council Directive 2010/63/EU and approved by the local Ethics Committee for Animal Experimentation.
Conflict of interest
The authors declare that they have no conflict of interest.
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