CHRONIC VERAPAMIL MODIFIES STRIATAL AND FRONTAL-CORTEX DOPAMINE LEVELS

In an attempt to elucidate if a change in dopamine (DA) levels was inv olved in the antimanic action of verapamil reported in various clinica l studies, monoamine concentrations in three brain regions (striatum, frontal cortex and hippocampus) obtained from verapamil-treated rats ( 10 mg/kg i.p. per day for 21 days) were quantified by HPLC coupled to electrochemical detection, and compared with monoamine concentrations in haloperidol-treated animals (5 mg/kg i.p. per day for 21 days). We have found that verapamil and haloperidol, when injected for 3 weeks t o rats sacrificed 2 h after the last injection, decreased the striatal DA concentration to a similar extent. This decrease was not observed in short-term (one injection 2 h before sacrifice) verapamil-or halope ridol-treated rats. Moreover, after such a single injection of verapam il the striatal DA concentration was even increased. The striatal conc entration of 3,4-dihydroxyphenylacetic acid (DOPAC) was increased abou t two-fold by haloperidol, but not by verapamil. This haloperidol-indu ced increase in striatal DOPAC was similar after one injection and aft er 21 days of haloperidol administration. Neither verapamil nor halope ridol modified the concentrations of homovanillic acid (HVA) or 3-meth oxytyramine (3-MT) in the striatum. In the frontal cortex, chronic ver apamil increased the concentrations of DA two-fold, and chronic halope ridol increased the concentration of DOPAC two-fold. The other DA meta bolites, namely HVA and 3-MT were not significantly changed. The conce ntration of serotonin (5-HT) and its main metabolite, 5-hydroxyindolea cetic acid (5-HIAA), in control, verapamil-and haloperidol-treated rat s were similar in the three brain regions studied. We conclude that DA autoreceptors are implicated in verapamil's effects on frontal cortex and striatum DA levels; and that the presumed antimanic action exerte d by verapamil is due to its long-term effect on these receptors. (C) 1998 Elsevier Science B.V./ECNP.