Dopamine D1 autoreceptor function: possible expression in developing rat prefrontal cortex and striatum.
Synthesis-modulating dopamine (DA) autoreceptor function was studied in vivo using gamma-butyrolactone (GBL) to block propagation along DA axons. DA synthesis was measured by the accumulation of L-3,4-dihydroxyphenylalanine (L-DOPA) after inhibition of aromatic L-amino acid decarboxylase. GBL treatment markedly increased DOPA accumulation in both the striatum and prefrontal cortex of developing rats. The selective DA partial D1 agonist SKF-38393 inhibited this GBL-induced rise in DA synthesis in both the striatum and prefrontal cortex of 15- and 22-day-old rats, but not in adults. The effects of SKF-38393 in developing rats were mimicked by the non-catechol D1 partial agonist CY-208-243, and were blocked by the D1 antagonist SCH-23390, suggesting receptor mediation. The mixed D2/D3 agonist quinpirole attenuated DA synthesis in striatum of both two-week-old and adult rats, but failed to inhibit the GBL-induced increase in DA synthesis in the developing prefrontal cortex. These findings suggest that synthesis-modulating D1-like receptor function may emerge transiently in the developing mammalian forebrain. In the adult striatum these functions appear to be subsumed by D2-like receptors, whereas all synthesis-modulating DA receptor function in prefrontal cortex appears to be essentially lost with maturation.
Department of Psychiatry, Harvard Medical School, McLean Hospital, Belmont, MA 02178.
M H
MH
Teicher
A L
AL
Gallitano
H A
HA
Gelbard
H K
HK
Evans
E R
ER
Marsh
R G
RG
Booth
R J
RJ
Baldessarini
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000254:growth & development / Q000502:physiology*; D003342:Corpus Striatum / Q000187:drug effects / Q000254:growth & development / Q000502:physiology*; D004295:Dihydroxyphenylalanine / Q000378:metabolism; D015259:Dopamine Agents / Q000494:pharmacology; D004873:Ergolines / Q000494:pharmacology; D005260:Female; D007211:Indoles / Q000494:pharmacology; D008297:Male; D010617:Phenanthridines / Q000494:pharmacology; D019257:Quinpirole; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000502:physiology*; D017447:Receptors, Dopamine D1
D015259:Dopamine Agents; D004873:Ergolines; D007211:Indoles; D010617:Phenanthridines; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; C054531:CY 208-243; D019257:Quinpirole; D004295:Dihydroxyphenylalanine; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine