New Findings on How Morphine Works in the Brain

Eliminating RGS7, a brain protein inhibitor, enhanced reward behavior, analgesic effect and withdrawal response and delayed tolerance according to “Regulator of G-Protein Signaling 7 Regulates Reward Behavior by Controlling Opioid Signaling in the Striatum,” published ahead of print in August in Biological Psychiatry. Dissecting central-specific actions, lead author Laurie P. Sutton—Ph.D, The Scripps Research Institute, Jupiter, Fla.—and her team ascertained that RGS7 may regulate morphine behavior through nucleus accumbens neurons.

Morphine, part of the G-protein-coupled receptors family, mediates euphoria and analgesia through the u-opiod receptor. Methods to assess analgesia, tolerance and physical dependence included conditioned place preference and self-administration paradigms. Electrophysiology determined RGS7’s influence on morphine-induced neuronal excitability and glutamatergic synapses.

Genetic approaches to ablate G-protein signaling of RGS7, globally and in specific neuronal populations, developed an “encompassing model,” which suggests multiple synaptic mechanisms contribute to morphine-mediated reward behavior, notes the study. Dissociating circuit-specific action, gave “a better understanding of the molecular mechanism involved in diverse actions of morphine use,” it adds.

Researchers call RGS7 in striatal neurons “selectively responsible for rewarding and reinforcing behaviors to morphine without effecting analgesia, tolerance and withdrawal.” RGS7 deletion in dopaminergic neurons didn’t influence morphine reward, they say. G-protein signaling may regulate GPCR, they add.