THE EFFECTS OF SEROTONIN BIOSYNTHESIS INHIBITION ON NICOTINE AND NIFEDIPINE-INDUCED ANALGESIA IN RATS

The calcium channel blocker nifedipine has analgesic properties that a re enhanced by nicotine. Although it is not known how this analgesic s tate might affect the awareness of anginal pain and impending myocardi al infraction, recent studies have shown an increased mortality associ ated with the use of large doses of nifedipine. Because both nifedipin e- and nicotine-induced analgesia involve serotonergic mechanisms, we studied the effects of the serotonin biosynthesis inhibitor parachloro phenylalanine (pCPA) on nifedipine- and nicotine-induced analgesia. No ciception was assessed by tail-flick method. Rats pretreated with pCPA (300 mg/kg intraperitoneally [IP]) followed by either nifedipine (15 mg/kg IF) or nicotine (1 mg/kg subctaneously) had a increase in tail-f lick latency of 41% (P = 0.09) and 50% (P = 0.05), respectively, compa red with animals that did not receive pCPA. Additionally, rats pretrea ted with pCPA followed by a combination of nicotine and nifedipine dou bled their tail-flick latency (P = 0.0001) compared with animals that were not treated with pCPA. These data further support the involvement of the serotonergic system in both nifedipine- and nicotine-induced a nalgesia and suggest that drugs that affect serotonin levels, includin g tricyclic antidepressants and serotonin-specific reuptake inhibitors , may also affect the analgesia induced by nifedipine and nicotine. Im plications: This study examines the effect of serotonin depletion on n icotine and nifedipine-induced analgesia. Nifidipine is a calcium chan nel blocker used to treat high blood pressure. It also has pain-reliev ing properties that are enhanced by nicotine. Because both nifedipine and nicotine-induced analgesia involve the neurotransmitter serotonin, it is important to know how changes in serotonin concentration might affect both nicotine and nifedipine-induced analgesia. This study not only supports the involvement of the serotonergic system in both nifid ipine- and nicotine-induced analgesia, but also suggests that drugs th at affect serotonin levels may also affect analgesia induced by nifidi pine and nicotine.