Exploring pharmacological inhibition of G as an analgesic strategy.

Background And Purpose: Misuse of opioids has greatly affected our society. One potential solution is to develop analgesics that act at targets other than opioid receptors. These can be used either as stand-alone therapeutics or to improve the safety profile of opioid drugs.

Members of the KCTD family are major regulators of cAMP signaling.

Cyclic adenosine monophosphate (cAMP) is a pivotal second messenger with an essential role in neuronal function. cAMP synthesis by adenylyl cyclases (AC) is controlled by G protein-coupled receptor (GPCR) signaling systems. However, the network of molecular players involved in the process is incompletely defined.

Gut Microbial Signatures Can Discriminate Unipolar from Bipolar Depression.

Discriminating depressive episodes of bipolar disorder (BD) from major depressive disorder (MDD) is a major clinical challenge. Recently, gut microbiome alterations are implicated in these two mood disorders; however, little is known about the shared and distinct microbial characteristics in MDD versus BD. Here, using 16S ribosomal RNA (rRNA) gene sequencing, the microbial compositions of 165 subjects with MDD are compared with 217 BD, and 217 healthy controls (HCs).

Intranasal administration of a stapled relaxin-3 mimetic has anxiolytic- and antidepressant-like activity in rats.

Background And Purpose: Depression and anxiety are common causes of disability, and innovative tools and potential pharmacological targets are actively sought for prevention and treatment. Therapeutic strategies targeting the relaxin-3 peptide or its primary endogenous receptor, RXFP3, for the treatment of major depression and anxiety disorders have been limited by a lack of compounds with drug-like properties. We proposed that a hydrocarbon-stapled mimetic of relaxin-3, when administered intranasally, might be uniquely applicable to the treatment of these disorders.

Effects of haloperidol on cognitive function and behavioural flexibility in the IntelliCage social home cage environment.

This study examined the effects of chronic administration of haloperidol in female C57BL/6 mice. As patients with schizophrenia often show perseverant behaviours and lack of behavioural flexibility, it is important to know whether the effect of haloperidol makes these traits worse. This study, therefore, was designed to evaluate the effects of haloperidol on the learning performance of mice using an automated home cage environment, the IntelliCage.

(R)-fluoxetine enhances cognitive flexibility and hippocampal cell proliferation in mice.

Fluoxetine is a clinically successful antidepressant. It is a racemic mixture of (R) and (S) stereoisomers. In preclinical studies, chronic treatment with fluoxetine (10 mg/kg) had antidepressant effects correlated with increased hippocampal cell proliferation in adult rodents.

Relaxin' the brain: a case for targeting the nucleus incertus network and relaxin-3/RXFP3 system in neuropsychiatric disorders.

Unlabelled: Relaxin-3 has been proposed to modulate emotional-behavioural functions such as arousal and behavioural activation, appetite regulation, stress responses, anxiety, memory, sleep and circadian rhythm. The nucleus incertus (NI), in the midline tegmentum close to the fourth ventricle, projects widely throughout the brain and is the primary site of relaxin-3 neurons. Over recent years, a number of preclinical studies have explored the function of the NI and relaxin-3 signalling, including reports of mRNA or peptide expression changes in the NI in response to behavioural or pharmacological manipulations, effects of lesions or electrical or pharmacological manipulations of the NI, effects of central microinfusions of relaxin-3 or related agonist or antagonist ligands on physiology and behaviour, and the impact of relaxin-3 gene deletion or knockdown.

Hydrocarbon stapled B chain analogues of relaxin-3 retain biological activity.

Relaxin-3 or insulin-like peptide 7 (INSL7) is the most recently discovered relaxin/insulin-like family peptide. Mature relaxin-3 consists of an A chain and a B chain held by disulphide bonds. According to structure activity relationship studies, the relaxin-3 B chain is more important in binding and activating the receptor.