Dopamine (DA) autoreceptor efficacy of 3-PPP enantiomers after short-term synaptic DA deprivation.
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.
Hjorth
S
S
Department of Pharmacology, University of Göteborg, Sweden.
Clark
D
D
Carlsson
A
A
D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004295:Dihydroxyphenylalanine / Q000096:biosynthesis; D004298:Dopamine / Q000502:physiology*; D008032:Limbic System / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects*; D012110:Reserpine / Q000494:pharmacology; D013237:Stereoisomerism; D013569:Synapses / Q000187:drug effects / Q000502:physiology*
D000978:Antiparkinson Agents; D010880:Piperidines; D011954:Receptors, Dopamine; D004295:Dihydroxyphenylalanine; D012110:Reserpine; C026539:preclamol; D004298:Dopamine