Prenatal exposure to cocaine selectively reduces D1 dopamine receptor- mediated activation of striatal Gs proteins

H. Y. Wang, S. Runyan, E. Yadin, E. Friedman

Research output: Contribution to journalArticlepeer-review

Abstract

The effect of in utero exposure to cocaine on striatal dopamine receptors was assessed at postnatal days 10 through 100 by examining receptor-mediated increases in GTP binding to Gα proteins. Pregnant Dutch-belted rabbits were injected with 4 mg/kg i.v. of cocaine HCl twice a day on gestational days 8 through 29, and striatal membranes were prepared from their progenies on days 10 through 100. Dopamine-stimulated [35S]GTPγS binding to membrane α subunits was measured and found to increase binding to Gαs and Gαi. Pharmacological characterization of the dopamine response revealed that enhanced [35S]GTPγS binding to Gαs is associated with D1 receptor stimulation, whereas binding to Gαi is linked to D2 receptor activation. The abilities of dopamine to stimulate the binding of [35S]GTPγS to Gαs but not to Gαi was reduced in striata obtained from cocaine-exposed animals when examined at 10, 50 or 100 days of age. Similarly, prenatal cocaine exposure also reduced dopamine-stimulated [α-32P]GTP binding to Gαs without influencing binding to Gαi. Fetal cocaine exposure did not change carbachol-induced increases in [35S]GTPγS binding to Gαi and Gαo. Immunoblot analyses showed no changes in the amounts of these α subunits in membranes from cocaine-exposed animals vs. controls. Moreover, prenatal cocaine did not affect [3H]SCH23390 binding to D1 dopamine receptors in the caudate, putamen or substantia nigra. The results suggest that prenatal exposure of rabbits to cocaine selectively desensitizes the response to D1 dopamine receptor stimulation. This effect was observed on postnatal day 10 and persisted up to 100 days of age.

Original languageEnglish
Pages (from-to)492-498
Number of pages7
JournalJournal of Pharmacology and Experimental Therapeutics
Volume273
Issue number1
StatePublished - 1995
Externally publishedYes

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