Comparison of the acute actions of amine-depleting drugs and dopamine receptor antagonists on dopamine function in the brain in rats

Abstract

The effects of the monoamine depleting drugs oxypertine, tetrabenazine and reserpine were compared with those of the dopamine receptor antagonists, chlorpromazine and trifluoperazine, on behavioural and biochemical indices of dopamine function in the brain. Oxypertine (0.625–20 mg/kg, i.p.), chlorpromazine (0.625–20 mg/kg i.p.) and trifluoperazine (0.0625–2.0 mg/kg i.p.), administered to rats 1 hr previously, inhibited stereotyped behaviour induced by both amphetamine (5.0 mg/kg i.p.) and apomorphine (1.0 mg/kg, s.c.) in a dose-dependent manner. Tetrabenazine (0.625–20 mg/kg i.p., l hr previously) inhibited stereotypy induced by amphetamine but not that induced by apomorphine. Reserpine (0.1–10 mg/kg i.p., 6 hr previously) did not inhibit, but in larger doses, tended to enhance the stereotyped responses to both amphetamine and apomorphine. Oxypertine (10 mg/kg, i.p., 1 hr previously), tetrabenazine (5 mg/kg i.p., 1 hr previously) and reserpine (2.5 mg/kg i.p., 6 hr previously) reduced the content of dopamine in the striatum but increased the concentrations of homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC). Chlorpromazine (5 mg/kg i.p.) and trifluoperazine (0.5 mg/kg i.p.), given 1 hr previously, did not alter concentrations of dopamine in the striatum but increased those of HVA and DOPAC. Oxypertine, chlorpromazine and trifluoperazine weakly inhibited dopamine-stimulated adenylate cyclase in homogenates of the striatum in the rat. Tetrabenazine and reserpine had no effect. Similarly, trifluoperazine and chlorpromazine displaced the specific binding of [ 3H]piflutixol to membranes from the striatum. Oxypertine also was weakly effective, but tetrabenazine and reserpine were without effect. Trifluoperazine, chlorpromazine and oxypertine displaced specific binding of [ 3H]spiperone and [ 3 H]N,n- propylnorapomorphine (NPA) to preparations of the striatum. Tetrabenazine was only weakly active and reserpine was without effect. In conclusion, oxypertine, like chlorpromazine and trifluoperazine, appears to cause blockade of post-synaptic dopamine receptors. Reserpine and tetrabenazine appear to act selectively by altering release of monoamines.