Abstract

The effects of d-amphetamine on the spontaneous and electrically evoked release of [3H]dopamine in slices of the rabbit caudate nucleus were investigated. At a concentration of 0.1 microM amphetamine did not modify the spontaneous outflow of radioactivity, but significantly inhibited the release of [3H]dopamine elicited by electrical stimulation. At a 10-fold higher concentration (1 microM) amphetamine enhanced the spontaneous outflow of radioactivity and also inhibited the stimulation-evoked release of [3H]dopamine. The inhibition by amphetamine of electrically evoked release of [3H]dopamine was also observed under conditions in which monoamine oxidase was inhibited by pargyline. At concentrations of 0.1 and 0.5 microM amphetamine there was no inhibition of neuronal uptake and retention of [3H]dopamine in slices of the rabbit caudate. In the presence of 100 microM l-3-iodotyrosine, the inhibition by amphetamine of [3H]dopamine release was still obtained. The dopamine receptor antagonists, haloperidol and sulpiride, were not able to antagonize the inhibition by amphetamine of the electrically evoked release of [3H] dopamine 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] dopamine. Nomifensine, an inhibitor of neuronal uptake of dopamine prevented the release of [3H]dopamine induced by exposure to 10 microM amphetamine and antagonized the inhibitory effects of lower concentrations of amphetamine on the electrically evoked release of [3H]dopamine. Tyramine and amfonelic acid in low concentrations enhanced the spontaneous outflow of radioactivity and, similarly to amphetamine, inhibited the electrically evoked release of [3H]dopamine. Exposure to bretylium (1 and 10 microM) inhibited the release of [3H]dopamine elicited by electrical stimulation. In the presence of bretylium, the inhibition by amphetamine of the stimulation-evoked release of [3H]dopamine was still present. In contrast to its inhibitory action on the release of [3H]dopamine, exposure to amphetamine (0.1-1.0 microM) enhanced in a concentration-dependent manner the electrically evoked release of [3H]norepinephrine from the rabbit hypothalamus. These results indicate that the inhibition by amphetamine of the electrically evoked release of [3H]dopamine does not involve the activation of presynaptic inhibitory dopamine autoreceptors possibly located on dopaminergic nerve terminals.(ABSTRACT TRUNCATED AT 400 WORDS)