Chronic verapamil modifies striatal and frontal cortex dopamine levels.

Abstract

In an attempt to elucidate if a change in dopamine (DA) levels was involved in the antimanic action of verapamil reported in various clinical 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 to 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 haloperidol-treated rats. Moreover, after such a single injection of verapamil the striatal DA concentration was even increased. The striatal concentration of 3,4-dihydroxyphenylacetic acid (DOPAC) was increased about two-fold by haloperidol, but not by verapamil. This haloperidol-induced increase in striatal DOPAC was similar after one injection and after 21 days of haloperidol administration. Neither verapamil nor haloperidol modified the concentrations of homovanillic acid (HVA) or 3-methoxytyramine (3-MT) in the striatum. In the frontal cortex, chronic verapamil increased the concentrations of DA two-fold, and chronic haloperidol increased the concentration of DOPAC two-fold. The other DA metabolites, namely HVA and 3-MT were not significantly changed. The concentration of serotonin (5-HT) and its main metabolite, 5-hydroxyindoleacetic acid (5-HIAA), in control, verapamil- and haloperidol-treated rats 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 exerted by verapamil is due to its long-term effect on these receptors.