Activation of dopamine D3 autoreceptors inhibits firing of ventral tegmental dopaminergic neurones in vivo.
The firing rate of dopaminergic neurones in the ventral tegmental area of anaesthetised rats was dose-dependently (0.31-5.0 micrograms/kg i.v.) inhibited by the dopamine D3 receptor agonist, (+)-7-OH-DPAT (7-hydroxy-2-(di-n-propylamino)tetralin). The selective dopamine D3 receptor antagonist, (+)-S 14297 ((+)-[7-(N,N-dipropylamino)-5,6,7,8-tetrahydro-naphtho(2,3b)dihydro,2,3- furane]), dose-dependently (16-125 micrograms/kg i.v.) inhibited the action of (+)-7-OH-DPAT (5 micrograms/kg i.v.); its inactive distomer, (-)-S 17777 (125 micrograms/kg i.v.), was ineffective. Alone, (+)-S 14297 (125 micrograms/kg i.v.) did not modify the firing rate. Haloperidol (16 micrograms/kg i.v.) fully reversed the action of (+)-7-OH-DPAT and, alone, significantly increased firing rate. These data suggest that inhibitory (dendritic) dopamine D3 (auto)receptors control the electrical activity of ventral tegmental area-localised dopaminergic neurones.
Lejeune
F
F
Institut de Recherches Servier, Centre de Recherches de Croissy, Croissy-sur-Seine, France.
Millan
M J
MJ
D015081:2-Naphthylamine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D017660:Autoreceptors / Q000502:physiology*; D005663:Furans / Q000494:pharmacology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011954:Receptors, Dopamine / Q000502:physiology*; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D017557:Ventral Tegmental Area / Q000502:physiology*
D017660:Autoreceptors; C493595:Drd3 protein, rat; D005663:Furans; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D013764:Tetrahydronaphthalenes; C090812:7-(N,N-dipropylamino)-5,6,7,8-tetrahydronaphtho(2,3-b)dihydro-2,3-furan; D015081:2-Naphthylamine; C031349:7-hydroxy-2-N,N-dipropylaminotetralin