Dopamine (DA) autoreceptor efficacy of 3-PPP enantiomers after short-term synaptic DA deprivation

Eur J Pharmacol. 1988 Aug 2;152(3):207-15. doi: 10.1016/0014-2999(88)90715-7.


We have compared the central dopamine (DA) autoreceptor-stimulatory properties of the 'atypical' DA agonist, (-)-3-PPP, its (+)-antipode and the reference DA agonist, apomorphine, following a 5 or an 18 h interruption of synaptic dopaminergic transmission by means of reserpine. The results are consistent with the notion that even a relatively short period (18 h) of synaptic DA deprivation results in a functional 'supersensitivity' of central DA synthesis-modulating autoreceptors. Interestingly, the data demonstrate a clearcut and significant enhancement of the intrinsic agonist efficacy of (-)-3-PPP in limbic and striatal parts after an 18 h as compared to a 5 h reserpine-induced impairment of synaptic DA transmission. In addition, there was a tendency towards a reduction in the doses of apomorphine and the 3-PPP enantiomers needed to inhibit DA synthesis in 18 vs. 5 h reserpinized rats in both brain regions. The findings indicate that the adaptive state of the DA autoreceptors had been altered, tentatively as a result of the reduced (endogenous) agonist occupancy. This is consistent with the suggestion that DA autoreceptors are influenced by a certain, albeit presumably low, endogenous dopaminergic tone under in vivo physiological conditions. The data obtained provide further support for the contention that receptor responsiveness is a critical determinant of the intrinsic efficacy displayed by DA receptor agonists such as (-)-3-PPP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiparkinson Agents / pharmacology*
  • Behavior, Animal / drug effects
  • Brain / drug effects
  • Brain / metabolism
  • Brain Chemistry / drug effects
  • Corpus Striatum / drug effects
  • Corpus Striatum / metabolism
  • Dihydroxyphenylalanine / biosynthesis
  • Dopamine / physiology*
  • Limbic System / drug effects
  • Limbic System / metabolism
  • Male
  • Motor Activity / drug effects
  • Piperidines / pharmacology*
  • Rats
  • Rats, Inbred Strains
  • Receptors, Dopamine / drug effects*
  • Reserpine / pharmacology
  • Stereoisomerism
  • Synapses / drug effects
  • Synapses / physiology*


  • Antiparkinson Agents
  • Piperidines
  • Receptors, Dopamine
  • Dihydroxyphenylalanine
  • Reserpine
  • preclamol
  • Dopamine