Morphine‐induced reciprocal alterations in Gαs and opioid peptide mRNA levels in discrete brain regions

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Abstract
The mechanisms involved in the development of morphine tolerance and dependence are still unknown. Recently much attention has been directed toward the changes in post receptor events. Opiate receptors, like other hormone and neurotransmitter receptors, have been shown to mediate their effects through guanine nucleotide binding proteins (G-proteins). This, in turn, may cause alterations in intracellular events, one of which is transcription of specific genes. We investigated the changes in the levels of mRNA of proenkephalin (PPE) and prodynorphin (DYN) and the stimulatory G protein alpha subunit (Gαs) in adult morphine tolerant rats. Chronic morphine treatment induced reciprocal alterations in the levels of opioid peptide mRNA and Gαs in discrete brain regions. In striatum, PPE mRNA decreased by 49% (P < .01) and in hypothalamus. DYN mRNA showed a decrease of 21% (P < .01). In contrast, Gαs mRNA increased 20% (P < .01) in striatum and 97% (P < .01), in hypothalamus. In hippocampus the changes were reversed: PPE mRNA increased (55%, P <.05) and Gαs mRNA decreased (33%, P < .01). Frontal cortex exhibited a samll decrease in PPE (11.5%, P <.05) without any change on Gαs or DYN mRNA levels. These reciprocal alterations suggest an apposing mode of regulation of Gαs and PPE/DYN gene expression in morphine tolerant animals.