The effects of single and repeated morphine administration on the level of thyrotropin-releasing hormone and its receptors in the rat brain

Abstract

Effects of single (20 mg/kg i.p.), and repeated morphine (increasing doses: from 20 to 100 mg/kg/day i.p., twice daily for 10 days) administration on the thyrotropin-releasing hormone (TRH) level and TRH receptors in discrete brain regions of the rat were investigated. As shown by a specific radioimmunoassay, a single dose of morphine increased the TRH level in the septum only. At 2 h after the last dose of repeated morphine, no significant changes in the TRH level were observed. At 72 h after the last morphine injection, the TRH level was increased in the striatum and hippocampus, but remained unchanged in the nucleus accumbens and septum. A radioreceptor assay showed that acute morphine had no effect on the density or affinity of TRH receptors in the brain regions studied. In contrast, repeated morphine increased the K d of TRH receptors in the striatum at 2 h (by ca 42%) and 72 h (by ca 26%), and in the nucleus accumbens at 72 h (by ca 26%) after the last drug injection. At 2 h after the last morphine injection, the B max of TRH receptors was decreased in the nucleus accumbens (by ca 41%) and unchanged in other structures, whereas at 72 h it was elevated by ca 27% and 49% in the striatum and hippocampus, respectively. The above results indicate that r epeated but not acute administration of morphine leads to long-lasting, region-specific changes in both the TRH level and receptors.