Electrophysiological analysis of paraventricular thalamic neurons co-expressing kappa and mu opioid receptors.

The paraventricular thalamus (PVT) is a central node in the integration of stress- and reward-related information that may serve as a pivotal site for opioid receptors to exert their effects. Kappa opioid receptors (KOPrs) and mu opioid receptors (MOPrs) have dissociable and opposing roles in circuits of stress and reward. Interestingly, both are highly expressed in the PVT, however it is not known how aversive KOPr and rewarding MOPr signalling converges to dictate PVT activity and, by proxy, whole brain effects.

Navacaprant, a novel and selective kappa opioid receptor antagonist, has no agonist properties implicated in opioid-related abuse.

Kappa opioid receptors (KORs) are implicated in the pathophysiology of various psychiatric and neurological disorders creating interest in targeting the KOR system for therapeutic purposes. Accordingly, navacaprant (NMRA-140) is a potent, selective KOR antagonist being evaluated as a treatment for major depressive disorder. In the present report, we have extended the pharmacological characterization of navacaprant by further demonstrating its selective KOR antagonist properties and confirming its lack of agonist activity at KORs and related targets involved in opioid-related abuse.

The microbiota-gut-brain axis in hippocampus-dependent learning and memory: current state and future challenges.

A fundamental shift in neuroscience suggests bidirectional interaction of gut microbiota with the healthy and dysfunctional brain. This microbiota-gut-brain axis has mainly been investigated in stress-related psychopathology (e.g.

Retrieval-Extinction and Relapse Prevention: Rewriting Maladaptive Drug Memories?

Addicted individuals are highly susceptible to relapse when exposed to drug-associated conditioned stimuli (CSs; "drug cues") even after extensive periods of abstinence. Until recently, these maladaptive emotional drug memories were believed to be permanent and resistant to change. The rediscovery of the phenomenon of memory reconsolidation-by which retrieval of the memory can, under certain conditions, destabilize the previously stable memory before it restabilizes in its new, updated form-has led to the hypothesis that it may be possible to disrupt the strong maladaptive drug-memories that trigger a relapse.