Effects of Peripherally Acting Opioid Ligands on Central Opioid Receptors and <i>β</i>-Endorphin Release in Stressed Rats
- 1 P.K. Anokhin Research Institute of Normal Physiology RAMS, Moscow, Russia
- 2 P.K. Anokhin Research Institute of Normal Physiology RAMS, Moscow, Russia
- 3 P.K. Anokhin Research Institute of Normal Physiology RAMS, Moscow, Russia
- 4 P.K. Anokhin Research Institute of Normal Physiology RAMS, Moscow, Russia
Abstract
Using the radioreceptor binding assay, μ -opioid receptor (MOR) affinity in the midbrain of stressed rats was higher than in naive controls. MOR density in the rat frontal cortex was reduced after stress. Intragastric administration of the MOR antagonist naloxone methiodide was followed by an increase in the number of MORs in the frontal cortex. However, the MOR agonist loperamide significantly decreased the density of MORs in the frontal cortex and midbrain of naive animals. Loperamide and naloxone methiodide were shown to prevent an increase in MOR affinity and a decrease in MOR density in the midbrain of rats after restraint stress. The restraint stress was accompanied by an increase in the release of β -endorphin (BE) in the ventral tegmental area (VTA) of control rats. After administration, loperamide slightly decreased the release of BE, naloxone methiodide significantly increased the release of BE in the cingulate cortex (CC) of untreated animals, while drugs had no effect on the release of BE in the VTA. The drugs significantly increased the extracellular level of BE in the CC of stressed animals. Loperamide abolished the increase in the stress-induced release of BE in the VTA. By contrast, naloxone methiodide significantly increased the release of BE in the VTA of stressed rats. Our data indicated that activation of peripheral MORs induces depression of the central part of the μ -opioid system, but suppression of peripheral MOR activity induces activation of the central μ -opioid system, the interaction of which can be modulated by stress.
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