We investigated the relation between swimming exercise and fear memory extinction. Rats that performed regular swimming exercise over six weeks underwent a fear conditioning. Twenty-eight days later, they were submitted to extinction tests. Swimming rats had enhanced extinction process throughout the 5 days of the extinction test when compared to sedentary ones (Exercise vs. Fear Conditioning vs. Test days interaction effect. This suggests that the swimming exercise accelerated the process of aversive memory extinction, reducing the expression of conditioned fear behavior. These results encourage further studies addressing the anxiolytic effects of exercise, with potential implications for anxiety disorders such as post-traumatic stress disorder.

Early non-motor symptoms such as mood disorders and cognitive deficits are increasingly recognized in Parkinson's disease (PD). They may precede the characteristic motor symptomatology caused by dopamine (DA) neuronal loss in the substantia nigra pars compacta (SNc). It is well-known that striatal cholinergic interneurons (ChIs) are emerging as key regulators of PD motor symptom, however, their involvement in the cognitive and affective alterations occurring in the premotor phase of PD is poorly understood. We used optogenetic photoinhibition of striatal ChIs in mice with mild nigrostriatal 6-hydroxydopamine (6-OHDA) lesions and assessed their role in anxiety-like behavior in the elevated plus maze, social memory recognition of a congener and visuospatial object recognition. In transgenic mice specifically expressing halorhodopsin (eNpHR) in cholinergic neurons, striatal ChIs photoinhibition reduced the anxiety-like behaviour and reversed social and spatial short-term memory impairment induced by moderate DA depletion (e.g. 50% loss of tyrosine hydroxylase TH-positive neurons in the SNc). Systemic injection of telenzepine (0.3 mg/kg), a preferential M1 muscarinic cholinergic receptors antagonist, improved anxiety-like behaviour, social memory recognition but not spatial memory deficits. Our results suggest that dysfunction of the striatal cholinergic system may play a role in the short-term cognitive and emotional deficits of partially DA-depleted mice. Blocking cholinergic activity with M1 muscarinic receptor antagonists may represent a possible therapeutic target, although not exclusive, to modulate these early non-motor deficits. This article is protected by copyright. All rights reserved.

While the pathophysiology of several psychiatric disorders has become modestly elucidated in the last decade, comorbid sexual dysfunctions in such patients are frequently left apart from clinical and research interest. We aimed to address the malfunctioning neurocircuitry underlying sexual dysfunctions in depression, anxiety, schizophrenia and mania. We performed a comprehensive literature review, addressing any combination of the topics of "neurobiology"/"neural", "sexual"/"desire"/"arousal"/"orgasm"/"ejaculation" and "depression"/"anxiety"/"schizophrenia"/"mania"/"bipolar". Altered neurotransmitter levels or connectivity in patients are reported in sexual dysfunctions (either desire, arousal, orgasm and ejaculation) and main psychiatric disorders (depression, anxiety, mania and schizophrenia). Neuronal pathways responsible for the occurrence of sexual dysfunctions in psychiatric disorders can be  figured out by overlap  of their acknowledged pathophysiology. However, specific research in that group is scant, so future tailored studies are warranted to elucidate actual mechanisms.

Assessment of the impact of Jacobson Progressive Muscle Relaxation (PMR) on depression-anxiety-stress symptoms, sense of coherence, health-related quality of life and well-being in long-term unemployed people with anxiety disorders.

The purpose of this report is to review treatment options for patients with comorbid substance use disorder (SUD) and post-traumatic stress disorder, anxiety, or depression by comparing (1) concurrent treatments for SUD and the mental disorders with no treatment, usual care or active treatment for one condition only and (2) treatment for a single condition (SUD or the mental disorders) with no treatment, usual care or active treatment for the second disorder. Additionally, this review aims to review evidence-based guidelines regarding the treatments for patients with these comorbidities.

The error-related negativity (ERN) is an event-related potential in the electroencephalogram (EEG) observed within the first 100 ms after commission of an error. Increased ERN amplitudes have been observed in several psychological disorders characterized by high negative affect. While the ERN has extensively been studied in tasks using exteroceptive stimuli, its relation to interoceptive stimuli is unknown. Since errors related to interoception might be particularly relevant for survival and negative affect, this study aimed to explore the ERN for errors related to interoceptive, respiratory sensations (intERN). Moreover, we compared the intERN with a commonly observed ERN related to exteroceptive, visual stimuli (extERN) and examined their associations with interoception-related negative affect. We studied the ERN using a respiratory occlusion task (intERN) and a visual flanker task (extERN) in 40 healthy volunteers during continuous 129 channel EEG recordings. In the occlusion task, participants received inspiratory occlusions of two different durations and indicated whether each occlusion was short or long. In the Flanker task, participants indicated the direction of arrowheads. Interoception-related negative affect was assessed with the Anxiety Sensitivity Index. Comparable with the extERN, the intERN was observed at fronto-central scalp positions after error commission in the occlusion task, but it peaked significantly earlier than the extERN. Mean amplitudes of the intERN and extERN showed no significant difference and were not correlated. Moreover, higher levels of anxiety sensitivity were correlated with significantly greater amplitudes of the intERN, but with lower amplitudes of the extERN. The present results firstly demonstrate an error-related negativity EEG-potential that is related to interoceptive sensations (intERN). This intERN is not associated with a commonly observed ERN elicited by exteroceptive stimuli and is distinctly linked to higher levels of interoception-related negative affect. The intERN might be a promising neural marker for future studies on interoception, negative affect and error processing.

The discovery of extended catalytic versatilities is of great importance in both the chemistry and biotechnology fields. Fatty acid amide hydrolase (FAAH) belongs to the amidase signature superfamily and is a major endocannabinoid inactivating enzyme using an atypical catalytic mechanism involving hydrolysis of amide and occasionally ester bonds. FAAH inhibitors are efficacious in experimental models of neuropathic pain, inflammation and anxiety, among others. We report a new multi-target drug, AGN220653, containing a carboxyamide-4-oxazole moiety and endowed with efficacious analgesic and anti-inflammatory activities, which are partly due to its capability of achieving inhibition of FAAH, and subsequently increasing the tissue concentrations of the endocannabinoid anandamide. This inhibitor behaves as a non-competitive, slowly reversible inhibitor. Autoradiography of purified FAAH incubated with AGN220653, opportunely radiolabeled, indicated covalent binding followed by fragmentation of the molecule. Molecular docking suggested a possible nucleophilic attack by FAAH-Ser241 on the carbonyl group of the carboxyamide-4-oxazole moiety, resulting in the cleavage of the C-C bond between the oxazole and the carboxyamide moieties, instead of either of the two available amide bonds. MRM-MS analyses only detected the Ser241-assisted formation of the carbamate intermediate, thus confirming the cleavage of the aforementioned C-C bond. Quantum mechanics calculations were fully consistent with this mechanism. The study exemplifies how FAAH structural features and mechanism of action may override the binding and reactivity propensities of substrates. This unpredicted mechanism could pave the way to the future development of a completely new class of amidase inhibitors, of potential use against pain, inflammation and mood disorders.