Abstract

Amphetamine (AMPH) inhibits the electrically evoked release of [3H]acetylcholine (ACh) from rat striatal slices through the activation of inhibitory dopamine receptors. Naturally occurring analogs of amphetamine (AMPH) such as beta-phenylethylamine (beta-PEA), tyramine (TYR) and octopamine (OCT) are present in trace amounts in the brain of several species. We have studied in this model, in comparison with AMPH, the effects of beta-PEA, TYR and OCT, in order to explore if their central effects are mediated through an action involving dopaminergic nerve terminals or whether they activate a specific receptor directly. In contrast to the results obtained with AMPH, in the absence of inhibition of monoamine oxidase activity, the three amines beta-PEA (0.1-10 microM), TYR (0.1-10 microM) and OCT (10 microM) did not affect the electrically evoked release of [3H]ACh. On the other hand, in the presence of pargyline (10 microM), the three amines inhibited the electrically evoked release of [3H]ACh and all subsequent experiments were carried out in the presence of pargyline. After pretreatment with reserpine (5 mg/kg s.c., 24 h), which results in a 95% depletion of the endogenous dopamine content, OCT lost its inhibitory effect on [3H]ACh release, whereas beta-PEA and TYR still inhibited the electrically evoked release of [3H]ACh. Reserpine pretreatment (5 mg/kg s.c., 24 h) combined with alpha-methyl-p-tyrosine (300 mg/kg i.p., 2 h) reduced endogenous dopamine levels by 99.9%, but, under these conditions, beta-PEA, TYR and AMPH still retained their inhibitory effect on [3H]ACh, release. These inhibitory effects of beta-PEA and AMPH on [3H] ACh release were antagonized by S-sulpiride (0.1 microM). In striatal slices from untreated rats, the inhibition of [3H]ACh released by beta-PEA (30 microM), TYR (30 microM) or AMPH (10 microM) was abolished completely after a 6-hydroxydopamine lesion of the nigro-striatal dopaminergic system. The present data indicate that in order to inhibit the release of [3H]ACh from rat striatal slices in vitro, OCT requires the integrity of vesicular stores of dopamine. On the other hand, beta-PEA, TYR and AMPH are still active when the dopamine levels are depleted, although they require the integrity of the dopaminergic nerve terminal. Inhibition of monoamine oxidase is essential to demonstrate the inhibitory effects of exogenous beta-PEA, TYR and OCT on cholinergic transmission. Our results indicate that a hypothesis concerning a possible physiopathological role of endogenous beta-PEA or TYR should involve concomitant changes in monoamine oxidase activity.