Abstract |
Drug addiction is considered to be a major social-economic issue since it is characterized as a disease that currently affects more than 30 million people in the USA and Europe. Although, scientists have elucidate the involvement of several brain regions and signaling pathways that are involved in drug of abuse actions, still drug dependence pathways have not been fully characterized. In particular, members of the regulators of G protein signaling (RGS) have been implicated in addiction, with a particular interest of RGS9-2 having an essential role in opiate dependence, regarding its expression in nucleus accumbens. In this present study, RGS9-
2 role is investigated in determination of proximal and distal dendritic spine density in neuronal population of dorsal striatum, (a region functionally related to elements of addiction) in locomotor morphine sensitization paradigm. Specifically, morphine leads to decreased proximal mushroom spine density in RGS9 knockout mice and in proximal/distal stubby density. Also, morphine affects spine morphology, regarding head and neck diameter of dendritic spines. More specifically, morphine administration results in decreased thin and stubby head diameter in proximal dendrites and in a decrease in total spine head diameter in distal dendrites. Moreover, proteins that are involved in synaptic and structural plasticity are also regulated by morphine administration in the dorsal striatum of RGS9 wild type mice, whereas aberrant regulation of synaptic proteins in response to morphine is observed in the dorsal striata knockout mice. Taken together, the present study elucidates opiate actions in synaptic plasticity and provides further evidence of a potent role of RGS9-2 in the molecular mechanisms underlying addiction.
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