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

Naunyn Schmiedebergs Arch Pharmacol. 1984 Aug;327(1):6-13. doi: 10.1007/BF00504984.

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)

MeSH terms

  • Acetylcholine / metabolism*
  • Animals
  • Corpus Striatum / drug effects*
  • Corpus Striatum / metabolism
  • Dextroamphetamine / pharmacology
  • Dopamine / metabolism*
  • Electric Stimulation
  • In Vitro Techniques
  • Male
  • Piperidines / pharmacology*
  • Rabbits
  • Rats
  • Rats, Inbred Strains
  • Receptors, Dopamine / drug effects
  • Stereoisomerism
  • Synaptic Transmission / drug effects*
  • Tritium

Substances

  • Piperidines
  • Receptors, Dopamine
  • Tritium
  • preclamol
  • Acetylcholine
  • Dextroamphetamine
  • Dopamine