Developmental differences in dopamine synthesis inhibition by (+/-)-7-OH-DPAT.
Dopamine synthesis modulation by the D2-family agonist (+/-)-7-OH-DPAT was explored in striatum, accumbens, and prefrontal cortex of 10-40 day old rats using the gamma-butyrolactone (GBL) autoreceptor model. GBL produced an age-dependent increase in dopamine synthesis that was inhibited by (+/-) 7-OH-DPAT (0.1-13.5 mg/kg) at all ages and antagonized by eticlopride in the nucleus accumbens and striatum. The ID50 of (+/-) 7-OH-DPAT increased with age, suggesting decreased autoreceptor sensitivity with maturation. In prefrontal cortex, (+/-) 7-OH-DPAT inhibited synthesis between 10-30 days, with no evidence of autoreceptor function at 40 days. Dopamine synthesis was also inhibited with the D3/D2 agonist quinpirole at 15 days of age in vivo and yielded similar results to those obtained with (+/-) 7-OH-DPAT. Finally, under conditions that result in low D2 receptor affinity, D3 specificity was examined in vitro at 15 days with (+/-) 7-OH-DPAT, which produced comparable (yet more potent) effects to those observed in vivo. These findings illustrate D3 autoreceptor-like activity in ascending dopamine regions and provide further support for transient prefrontal cortex autoreceptor-like function that recedes by puberty.
Andersen
S L
SL
Department of Psychiatry, Harvard Medical School, McLean Hospital, Belmont, MA 02178, USA.
Dumont
N L
NL
Teicher
M H
MH
D000367:Age Factors; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects; D004298:Dopamine / Q000096:biosynthesis*; D018491:Dopamine Agonists / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D005260:Female; D007980:Levodopa / Q000032:analysis; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D017397:Prefrontal Cortex / Q000187:drug effects; D019257:Quinpirole / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012457:Salicylamides / Q000494:pharmacology; D013764:Tetrahydronaphthalenes / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D012457:Salicylamides; D013764:Tetrahydronaphthalenes; D019257:Quinpirole; D007980:Levodopa; C045989:eticlopride; C031349:7-hydroxy-2-N,N-dipropylaminotetralin; D004298:Dopamine