Alterations in the spontaneous release of dopamine and the density of the DA D2 receptor mRNA after chronic postnatal exposure to cocaine.
The influence of cocaine administration on dopamine (DA) release and D2 dopamine receptor mRNA levels was examined in developing rat brain. In the rat pup, cocaine (25 mg/ kg SC) was administered daily from postnatal days 1-9 and extracellular DA measured 24 h after the last injection of cocaine, using in vivo micro dialysis. Twenty-four hours after discontinuing cocaine administration, a decrease in the extracellular concentration of DA of more than 100% was found in treated pups compared to control pups. Pups were tested on postnatal days 10-12, 20-21, or 35-36. After 1 month, basal release of DA returned to control levels. To examine the structural basis of the alteration in basal release of DA, in situ hybridization studies were performed to access the effect of chronic administration of cocaine on the mRNA encoding the D2 DA receptor. These preliminary studies, on postnatal day 10, indicate that drug treatment alters the developmental pattern of D2 mRNA. The changes in D2 mRNA expression were accompanied by delayed disaggregation of neostriatal cells and diminished growth of neostriatal neurons. These structural changes may lead to functional impairment in the development of dopamine target cells, thus altering the balance of synaptic and trophic effects of DA.
Howard
S G
SG
Department of Molecular and Medical Pharmacology, University of California, Los Angeles 90024, USA.
Fisher
R
R
Landry
C F
CF
D000818:Animals; D000831:Animals, Newborn; D003042:Cocaine / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D005260:Female; D017403:In Situ Hybridization; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D013997:Time Factors
D018765:Dopamine Uptake Inhibitors; D012333:RNA, Messenger; D017448:Receptors, Dopamine D2; D003042:Cocaine; D004298:Dopamine