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Neuroendocrine and Behavioral Effects of Flunarizine in Young and Old Rats

Neuroendocrine and behavioral effects following an acute or chronic treatment with the calcium antagonist, flunarizine, have been studied in young and old rats. Both in young and old rats, acute administration of flunarizine (2 mg/kg) failed to modify plasma prolactin (PRL) levels, as measured at 8.00 a.m., 4.00 p.m. and 12.00 p.m. A chronic treatment with flunarizine (0.5 mg/kg/day, for 20 days) in young rats was followed by a relevant, albeit statistically not significant, increase in plasma PRL levels, as measured at 8.00 a.m. and 4.00 p.m., and by a significant decrease at 12.00 p.m. A shift of nocturnal peak of plasma PRL levels from 12.00 p.m. to 4.00 a.m. was observed in these animals. A chronic treatment with flunarizine in old rats was followed by a significant increase in plasma PRL levels, as measured at 12.00 p.m. The acquisition of active avoidance behavior was studied in a shuttle-box test. Acute administration of flunarizine failed to change the performance of young and old rats in acquiring the behavioral response, as measured by the total number of conditioned avoidance responses (CARs) and the percentage of learners. When flunarizine was administered chronically, a decrease in CARs and learners was observed both in young and old rats. This was accompanied by a significant increase in the percentage of animals that froze during the acquisition session. No significant effect was found in young and old rats tested in a “despair” test after a chronic treatment with flunarizine.