Activation of the Mu-Delta Opioid Receptor Heteromers Blocks Morphine Rewarding Effects.

Background: Evidence has accumulated demonstrating the existence of opioid receptor heteromers, and recent data suggest that targeting these heteromers could reduce opioid side effects while retaining therapeutic effects. Indeed, CYM51010 characterized as a MOR (mu opioid receptor)/DOR (delta opioid receptor) heteromer-preferring agonist promoted antinociception comparable with morphine but with less tolerance. In the perspective of developing these new classes of pharmacological agents, data on their putative side effects are mandatory.

Morphine-Induced Dendritic Spine Remodeling in Rat Nucleus Accumbens Is Corticosterone Dependent.

Background: Chronic morphine treatments produce important morphological changes in multiple brain areas including the nucleus accumbens.

Methods: In this study, we have investigated the effect of chronic morphine treatment at a relatively low dose on the morphology of medium spiny neurons in the core and shell of the nucleus accumbens in rats 1 day after the last injection of a chronic morphine treatment (5 mg/kg once per day for 14 days). Medium spiny neurons were labeled with 1,1' dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate crystal and analyzed by confocal laser-scanning microscope.

Role of pharmacokinetic and pharmacodynamic parameters in neuroadaptations induced by drugs of abuse, with a focus on opioids and psychostimulants.

The purpose of this review is to illustrate the importance of pharmacodynamic and pharmacokinetic factors in the complexity of the behavioral and neurochemical adaptations that occur following chronic treatments with drugs of abuse, with a focus on opioids and psychostimulants. As these neuroadaptations are thought to contribute to the pathogenesis and persistence of addiction, it is important to well understand how they can be modulated. The experimental results clearly show that changes observed are depending on the binding properties of the ligands, drug administration patterns, brain structures considered, and withdrawal periods.

Role of mGlu7 receptor in morphine rewarding effects is uncovered by a novel orthosteric agonist.

Opiate dependence is a major health issue and despite the existence of opioid substitution treatment, relapse frequently occurs. Group III metabotropic glutamate (mGlu) receptors has received much attention as a putative target in ethanol and cocaine addiction, but no data on opiate addiction exist. So we investigated the role of group III mGlu receptors in morphine rewarding effects through the expression and the reinstatement of conditioned place preference (CPP) using a newly synthesized mGlu4/mGlu7 receptor orthosteric agonist, LSP2-9166.

Rewarding or aversive effects of buprenorphine/naloxone combination (Suboxone) depend on conditioning trial duration.

Buprenorphine is used as a sublingual medication in the treatment of opioid dependence. However, its misuse by i.v.