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Time-course effects of a single administration of cocaine on receptor binding and subunit mRNAs of GABA(A) receptors.

We investigated the time-course effects of a single administration of cocaine (20 mg/kg) on GABA(A) receptor binding labeled by t-[(35)S]butylbicyclophophorothionate (TBPS) and on several types of GABA(A) receptor subunit mRNAs in the rat brain by in vitro quantitative receptor autoradiography and in situ hybridization. The levels of alpha 1, beta 2, and beta 3 subunit mRNAs in several brain regions such as the cortex, cerebellum, and striatum were significantly decreased within 1 h, while beta 3 subunit mRNA was increased in the dentate gyrus. All of these changes were transient, occurring within 1 h after the injection of cocaine. In the cortex and cerebellum, the reduction in alpha1 subunit mRNA was followed by a significant decrease in [(35)S]TBPS receptor binding, which occurred 4 h after cocaine injection. These findings suggest that acute cocaine administration discretely regulates GABA(A) receptor subunit mRNA levels in several brain regions through a change in transcription or turnover rates of subunit mRNAs, which may be closely related to cocaine-induced behavioral abnormalities.