Evaluating the Role of Gαo in Morphine-Induced Locomotor Stimulation
Gateley, Jennifer Nicole
MetadataShow full item record
Morphine is a potent analgesic prescribed for the treatment of pain, but also possesses significant addiction liability. All physiological actions of morphine involve activation of the μ-opioid receptor (MOR), a member of the G protein coupled receptor (GPCR) family known to couple to inhibitory Gαi/o proteins. Although it has been demonstrated that MOR-Gαo coupling is important for morphine analgesia, it is unclear whether these complexes also play a role in other physiological effects of morphine. The goal of this study was to evaluate the contribution of Gαo to the locomotor stimulating effects of morphine. To do this, locomotor activity (LA) was assessed in response to acute or chronic morphine administration in mice with decreased Gαo protein expression (Gαo heterozygous knockout mice; HET). Following acute morphine treatment, HET mice demonstrated decreased LA in comparison with wild-type (WT) controls, indicating that Gαo mediates acute morphine locomotor stimulation. In contrast, chronic morphine treatment is known to produce locomotor sensitization, which is a progressive enhancement of the locomotor response upon repeated drug exposure and is thought to be related to addiction. To evaluate the role of Gαo in this process, a novel protocol for evaluating morphine-induced locomotor sensitization was established and used to assess differences between WT and HET mice. In these experiments both WT and HET mice exhibited sensitization following chronic morphine treatment, suggesting that Gαo does not play a role in behavioral sensitization. However, WT mice displayed enhanced G protein stimulation in the striata following chronic morphine treatment, indicating that behavioral sensitization may be mediated by changes in G protein activity.