The effect of chronic morphine and cocaine administration on the Gs and Go protein messenger RNA levels in the rat hippocampus.

The effects of single (20 or 50 mg/kg) and repeated morphine (14 days, rising doses: four days, 2 x 10 mg/kg; two days, 2 x 20 mg/kg; two days, 2 x 30 mg/kg; two days, 2 x 40 mg/kg and four days, 2 x 50 mg/kg i.p.) or cocaine (20 mg/kg i.p., once every hour for 3 h for one or five days) on the Gs alpha and Go alpha protein messenger RNA levels were investigated in the rat hippocampus. As shown by in situ hybridization immunocytochemistry and optical densitometry of autoradiograms, acute morphine (20 mg/kg) decreased the Gs alpha messenger RNA level and increased the Go alpha messenger RNA level in the dentate gyrus and CA1 hippocampal region. Repeated morphine administration significantly decreased the hippocampal Gs alpha messenger RNA level at 12, 24 and 48 h, and enhanced the Go alpha messenger RNA level in those areas at 12 and 24 h after the last injection. Repeated and acute cocaine administration decreased the Go alpha messenger RNA level in the CA3 region and increased it in the CA1 at various time points. Furthermore, in all hippocampal regions, acute, but not chronic, cocaine administration increased the Gs alpha mRNA level at 24 h, whereas chronic treatment significantly decreased that level at 48 h after the last dose. The data indicate that chronic morphine elevates the Go and attenuates the Gs protein biosynthesis at later time points in all regions of the hippocampal formation.(ABSTRACT TRUNCATED AT 250 WORDS)