AMPHETAMINE INHIBITS THE ELECTRICALLY EVOKED RELEASE OF [H-3]DOPAMINE FROM SLICES OF THE RABBIT CAUDATE

Abstract

The effects of d-amphetamine on the spontaneous and electrically evoked release of [3H]dopamine [DA] in slices of the rabbit caudate nucleus were investigated. At a concentration of 0.1 .mu.M amphetamine did not modify the spontaneous outflow of radioactivity, but significantly inhibited the release of [3H]DA elicited by electrical stimulation. At a 10-fold higher concentration (1 .mu.M) amphetamine enhanced the spontaneous outflow of radioactivity and also inhibited the stimulation-evoked release of [3H]DA. Inhibition by amphetamine of electrically evoked release of [3H]DA was also observed under conditions in which monoamine oxidase was inhibited by pargyline. At concentrations of 0.1 and 0.5 .mu.M amphetamine there was no inhibition of neuronal uptake and retention of [3H]DA in slices of the rabbit caudate. In the presence of 100 .mu.M l-3-iodotyrosine, the inhibition by amphetamine of [3H]DA release was still obtained. The DA receptor antagonists haloperidol and sulpiride were not able to antagonize the inhibition by amphetamine of the electrically evoked release of [3H]DA at concentrations which effectively blocked apomorphine-induced inhibition of stimulation-evoked release of the labeled neurotransmitter. Exposure to serotonin in the presence of an inhibitor of neuronal uptake did not modify the spontaneous outflow of radioactivity or the electrically evoked release of [3H]DA. Nomifensine, an inhibitor of neuronal uptake of DA prevented the release of [3H]DA induced by exposure to 10 .mu.M amphetamine and antagonized the inhibitory effects of lower concentrations of amphetamine on the electrically evoked release of [3H]DA. Tyramine and amfonelic acid in low concentrations enhanced the spontaneous outflow of radioactivity and, similarly to amphetamine, inhibited the electrically evoked release of [3H]DA. Exposure to bretylium (1 and 10 .mu.M) inhibited the release of [3H]DA elicited by electrical stimulation. In the presence of bretylium, the inhibition by amphetamine of the stimulation-evoked release of [3H]DA was still present. In contrast to its inhibitory action on the release of [3H]DA, exposure to amphetamine (0.1-1.0 .mu.M) enhanced in a concentration-dependent manner the electrically evoked release of [3H]norepinephrine from the rabbit hypothalamus. Evidently, the inhibition by amphetamine of the electrically evoked release of [3H]DA does not involve the activation of presynaptic inhibitory DA autoreceptors possibly located on dopaminergic nerve terminals. The mechanism of the inhibitory action of amphetamine on dopaminergic neurotransmission remains to be clarified. This effect of amphetamine may involve an intracellular site of action that is shared by tyramine and amfonelic acid. Amphetamine may displace releasable DA to a nonreleasable site and/or modify the specific activities of releasable pools of DA. Amphetamine enhances the electrically evoked release of [3H]norepinephrine, indicating that the drug has a differential action on dopaminergic and noradrenergic nerve terminals.