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

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.