Effects of single and long-term administration of nifedipine on dopamine-related behaviors

The effects of single (2.5 and 5.0 mg/kg) and long-term (2.5 mg/kg, twice daily, for 30 days) ip administration of nifedipine on open-field and apomorphine-induced stereotyped behavior were evaluated in young male Wistar rats (12-16 animals per group for the open-field studies and 7 animals per group for the stereotypy experiments). Administration of a single dose of nifedipine produced no changes in ambulation or rearing frequencies or in immobility duration in the open-field compared to controls. Similarly, treatment with a single dose of nifedipine did not modify apomorphine-induced stereotypy. Withdrawal from long-term nifedipine administration caused a significant increase only in rearing frequency 24 h after the last drug injection (with a mean +/- SEM frequency of 23.2 +/- 2.8 for the nifedipine group and of 14.7 +/- 2.0 for control rats, after 6-min observation). This enhancement of rearing frequency was no longer observed 48 h after abrupt nifedipine withdrawal (means +/- SEM: 15.0 +/- 2.2 and 19.6 +/- 2.7 for nifedipine-treated and control rats, respectively). The other open-field behavioral parameters and apomorphine-induced stereotypy (which was observed 96 h after nifedipine withdrawal) were not affected by long-term nifedipine treatment; for example, the sum of stereotypy scores (mean +/- SEM) was 26.9 +/- 3.0 for nifedipine-treated rats and 25.5 +/- 2.2 for vehicle-treated animals. The possible mechanisms underlying these results are discussed in light of the changes in dopaminergic neurotransmission induced by dihydropyridine calcium channel blockers.