Differential effects of the stereoisomers of 3PPP on dopaminergic and cholinergic neurotransmission in superfused slices of the corpus striatum.

Abstract

The two enantiomers of 3PPP were tested on the spontaneous and electrically-evoked release of 3H-dopamine from slices of the rabbit caudate nucleus and of 3H-acetylcholine (3H-ACh) from slices of the rat caudate nucleus. In caudate slices labelled with 3H-dopamine, exposure to (+)3PPP (0.1-1 microM) facilitated the spontaneous outflow of radioactivity with a concomitant inhibition of the electrically-evoked release of 3H-dopamine. In the presence of cocaine 10 microM, exposure to (+)3PPP (1 microM) inhibited the electrically evoked release of 3H-dopamine without modifying the spontaneous outflow of radioactivity. This inhibitory effect was not significantly antagonized by S-sulpiride 0.01 microM. Exposure to (+)3PPP 1 microM inhibited the electrically-evoked release of 3H-ACh, and this effect was not modified by pretreatment with reserpine alone, or in combination with alpha-methyl-p-tyrosine (alpha-MT). In contrast to the (+) enantiomer, exposure to (-)3PPP (0.1-1 microM) facilitated the electrically-evoked release of 3H-dopamine without affecting the spontaneous outflow of radioactivity. (-)3PPP antagonized the inhibitory effect of apomorphine on the electrically-evoked release of 3H-dopamine. Exposure to (-)3PPP 1 microM did not modify the spontaneous or the electrically-evoked release of 3H-ACh. Yet, this concentration of (-)3PPP antagonized significantly the inhibitory effect of 0.03 microM apomorphine, 1 microM d-amphetamine, and 1 microM (+)3PPP on the electrically-evoked release of 3H-ACh (-)3PPP (0.1-1 microM) was about 100 times less potent than S-sulpiride at antagonizing the inhibitory effect of apomorphine on the electrically-evoked release of 3H-ACh.(ABSTRACT TRUNCATED AT 250 WORDS)