RATIONALE Women with premenstrual dysphoric disorder (PMDD) appear to have altered central nervous system sensitivity to neuroactive steroid hormones, manifesting as affective symptoms and heightened arousal in the luteal phase of the menstrual cycle. In particular, women with PMDD appear less sensitive to allopregnanolone, a positive allosteric GABA-A receptor (GABA-A-R) modulator. OBJECTIVES This

RATIONALE The use of methcathinone (MCAT), a psychostimulant drug that can lead to long-term health risks and executive dysfunction, increased to an alarming rate in recent years. Impairments in low-level executive function have been reported in substance use disorder. However, little empirical evidence is available regarding high-level executive function (e.g., problem solving), which may act as a

Drugs of abuse including cannabis and inhalants impair risk/reward decision making. Cannabis use is often concurrent with inhalant intoxication; yet, preclinical studies investigating the role of endocannabinoids in inhalant misuse are limited. To address this gap in the literature, we used the well-validated probabilistic discounting task to assess risk/reward decision making in rodents following

RATIONALE Trace amine-associated receptor 1 (TAAR1) is a G protein-coupled receptor that has a particular role in regulating dopaminergic, serotonergic, and glutamatergic transmission. TAAR1 agonists have shown pro-cognitive activities. However, it remains largely unknown of the effects of TAAR1 agonists on memory performance. OBJECTIVES Here, by using the mice novel object recognition (NOR) test,

Rationale Mephedrone is a frequently overused drug of abuse that belongs to the group of novel psychoactive substances. Although its mechanism of action, as well as toxic and psychoactive effects, has been widely studied, the role of different factors that could contribute to the increased vulnerability to mephedrone abuse is still poorly understood. Objectives The aim of the presented study was to

Rationale Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by deficits in social communication and interaction and restricted, repetitive behaviors. The unmet medical need in ASD is considerable since there is no approved pharmacotherapy for the treatment of these deficits in social communication, interaction, and behavior. Cariprazine, a dopamine D3-preferring D3/D2 receptor

The pharmacological interventions available for individuals in the early stages of psychosis are extremely limited. For those at clinical high risk for psychosis, there is no licensed treatment available. For those with first-episode psychosis, all licensed antipsychotic medications act via dopamine D2 receptors. While treatment with antipsychotics is transformative in some patients, in others, it

Abstract Rationale In recent years, psychedelic substances with serotonergic mechanisms have accumulated substantial evidence that they may provide therapeutic benefits for people suffering with psychiatric symptoms. Psychiatric disorders targeted by these psychedelic-assisted therapies are managed with serotonergic drugs like selective serotonin reuptake inhibitors (SSRIs) as the current standard

Rationale Social support and opioid replacement therapy are commonly used to treat opioid withdrawal. Objective The present study tested the hypothesis that social housing and buprenorphine administration can restore wheel running depressed by morphine withdrawal in rats. Results Experiment 1 assessed disruptive side effects of buprenorphine and found that administration of low doses (3.2, 10, & 32 µg/kg

Rationale Job stress can lead to job burnout, and BDNF polymorphism has been found to be involved in its psychopathological mechanism. Research needs a better understanding of the important role of gene × environment (i.e., BDNF polymorphism × job stress) interaction on job burnout. Objective This study aimed to explore how BDNF rs6265 polymorphism may moderate the relationship between job stress and

Post-traumatic stress disorder (PTSD) is a serious stress-related neuropsychiatric disorder caused by major traumatic events. Abnormal activity of the locus coeruleus (LC)-noradrenergic system is related to the development of PTSD-like symptoms. Our previous studies have indicated that endoplasmic reticulum (ER) stress induced neuronal apoptosis of LC in rats with PTSD. The purpose of this study was

Rationale Ketamine may model aspects of schizophrenia arising through NMDA receptor activity deficits. Although acute ketamine can induce effects resembling both positive and negative psychotic symptoms, chronic use may be a closer model of idiopathic psychosis. Objectives We tested the hypotheses that ketamine users had lower brain volumes, as measured using MRI, and greater sub-threshold psychotic

Rationale Pre-clinical evidence implicates the GABAergic system in mediating the reinforcing effects of alcohol and offers a therapeutic target for alcohol use disorder (AUD). The orthosteric GABAB receptor agonist baclofen decreases alcohol self-administration in animals and alcohol use in humans; however side effects limit its utility. Pre-clinical evidence shows positive allosteric GABAB receptor

Rationale Reward-associated cues can trigger incentive motivation for reward and invigorate reward-seeking behaviour via Pavlovian-to-instrumental transfer (PIT). Glutamate signaling within the basolateral amygdala (BLA) modulates cue-triggered increases in incentive motivation. However, the role of BLA metabotropic group II glutamate (mGlu2/3) receptors is largely unknown. Objectives In Experiment

Rationale Endocannabinoids are well poised to regulate crosstalk between energy sensing of hunger and satiety and reward-driven motivation. Objectives Here, we aimed to unravel associations between plasma endocannabinoids and brain connectivity in homeostatic and reward circuits across hunger and satiety states. Methods Fifteen participants (7 females) underwent two counter-balanced resting-state functional

Rationale Prior studies have demonstrated statistically significant but subtle differences in brain function between patients with a history of substance dependence (SD) and control groups. Objectives The goal of the present study was to show that variability in brain activation over the trials of a cognitive task is more useful for revealing the putative impact of SD than analyses focusing on the

Alzheimer's disease (AD) is a most common neurodegenerative disorder worldwide. Because of its complex pathogenesis, the prevention and therapies of AD still are a severe challenge. Evidence suggested that crocin, the major component of saffron, exhibited neuroprotective effects in AD. As such, in this study, N2a/APP695swe cells were enrolled to investigate the effects of crocin on endogenous Aβ-induced

RATIONALE Reward-associated cues can promote maladaptive behavior, including risky decision-making in a gambling setting. A propensity for sign tracking over goal tracking-i.e., interaction with a reward-predictive cue rather than the site of reward-demonstrates an individual's tendency to transfer motivational value to a cue. However, the relationship of sign tracking to risky decision-making remains

RATIONALE Forgetting of fear memory is a current medical therapy for posttraumatic stress disorder (PTSD), and hippocampal long-term depression (LTD) may be the underlying mechanism. Neuregulin 1 (NRG1), a trophic factor, reportedly modulates memory consolidation and synaptic plasticity. METHODS Fear memory was assessed using contextual fear conditioning. Electrophysiology was used to measure LTD and

RATIONALE AND OBJECTIVE This study was undertaken to assess the modulating effects of (1) pre-exposure to repeated social disruption and (2) group testing on writhing associated with visceral pain induced by intraperitoneal administration of acetic acid. MATERIALS AND METHODS Six consecutive days of social disruption were used to prime for stress, while group testing referred to 3 mouse cage-mates

Adenosine A2A receptors are highly enriched in the basal ganglia system, a region that is functionally implicated in schizophrenia. Preclinical evidence suggests a cross-regulation between adenosine A2A and dopamine D2 receptors in this region and that it is linked to the sensitization of the dopamine system. However, the relationship between A2A receptor availability and schizophrenia has not been

BACKGROUND There is evidence that post-training exposure to nicotine, cocaine, and their conditioned stimuli (CS), enhance memory consolidation in rats. The present study assessed the effects of blocking noradrenergic and dopaminergic receptors on nicotine and cocaine unconditioned and conditioned memory modulation. METHODS Males Sprague-Dawley rats tested on the spontaneous object recognition task

RATIONALE Alzheimer's disease (AD) is an age-related neurodegenerative disease characterized by progressive cognitive dysfunction and memory impairment. G protein-coupled receptor 40 (GPR40) is expressed in brain in addition to periphery and is associated with cognitive function such as space orientation, memory, and learning. However, the effects and mechanisms of GPR40 agonist in improving the AD

Rationale Reduced inhibitory control is more pronounced during substance-related cue exposure among addicts. However, it is inconclusive whether smokers' inhibitory control would be impaired by smoking-related background. Furthermore, few studies explored whether the cigarette-specific disgust aroused by smoking warning images would alleviate the negative effect of smoking-related cues on smokers'

RATIONALE Tramadol is widely used for pain relief especially in seniors. However, long-term use of tramadol has serious adverse effects, including cognitive impairment. Besides its memory effects, already demonstrated in animals, a recent clinical report suggests that tramadol could also affect executive function in seniors. Several studies have hypothesized that the anti-muscarinic properties of tramadol

Rationale Tolerance to cannabinoids could limit their therapeutic potential. Male mice expressing a desensitization-resistant form (S426A/S430A) of the type-1 cannabinoid receptor (CB1R) show delayed tolerance to delta-9-tetrahydrocannabinol (∆9-THC) but not CP55,940. With more women than men using medical cannabis for pain relief, it is essential to understand sex differences in cannabinoid antinociception

Rationale Opioids are effective medications, but they have several key limitations including the development of tolerance, establishment of dependence, diversion for non-medical use, and the development of addiction. Therefore, any drugs which act in an additive or synergistic fashion with opioids to address medical applications have the potential to reduce opioid-related harms. Objectives To determine

Rationale Rates of depression and suicide increase with altitude. In our animal model, rats housed at moderate altitude vs. at sea level exhibit increased depressive symptoms in the forced swim test (FST) and lack of response to selective serotonin reuptake inhibitors (SSRIs). Depression and SSRI resistance are linked to disrupted serotonergic function, and hypobaric hypoxia may reduce the oxygen-dependent

Rationale Abnormal functioning of the inhibitory gamma-aminobutyric acid (GABA) and excitatory (glutamate) systems is proposed to play a role in the development of schizophrenia spectrum disorder. Although results are mixed, previous 1H-magnetic resonance spectroscopy (MRS) studies in schizophrenia and clinical high-risk samples report these metabolites are altered in comparison to healthy controls

Background Depression is a severe mental disorder. Unfortunately, more than half of patients with major depression disorder cannot achieve remission after initial treatment with an antidepressant. Geniposide, a bioactive iridoid glycoside isolated from Gardenia jasminoides Ellis, can ameliorate depressive-like behaviors in mice. However, the underlying mechanism is still not very clear. Methods The

Rationale Misuse of dextroamphetamine occurs in work and recreational contexts. While acute drug effects broadly predict abuse liability, few studies have considered the relationship between acute effects and context. Objectives This study examined how individual differences in acute effects of dextroamphetamine relate to desire to take dextroamphetamine again in different contexts. Methods This secondary

A Correction to this paper has been published: https://doi.org/10.1007/s00213-021-05891-y

Rationale Anxiety, a negative state of high arousal and vigilance, is especially prevalent in women, making identification of underlying mechanisms critical for developing effective therapies. With the challenge of disentangling biological and social factors in humans, animal tests can provide valuable insights, although such tests, developed in males, have unclear validity for females. Objective To

With respect to Guo’s inspiring article (Guo et al. 2021), we would like to suggest several corrections about some of the figures. We felt obliged to write this erratum letter as these incompatibilities may cause confusion for the readers.

Background Work in humans has shown that impulsivity can be advantageous in certain settings. However, evidence for so-called functional impulsivity is lacking in experimental animals. Aims This study investigated the contexts in which high impulsive (HI) rats show an advantage in performance compared with mid- (MI) and low impulsive (LI) rats. We also assessed the effects of dopaminergic and noradrenergic

Aims Intravenous (IV) misuse of the µ opioid analgesic oxymorphone has caused significant public health harms; however, no controlled data on its IV abuse potential are available. The primary aims of this pilot study were to directly compare IV oxymorphone to IV oxycodone, morphine, and hydromorphone on a subjective measure of drug liking and to assess relative potency. Methods Participants (n = 6)

Rationale Emotion recognition is impaired in drug addiction. However, research examining the effects of cocaine use on emotion recognition yield mixed evidence with contradictory results potentially reflecting varying abstinence durations. Objectives Therefore, we investigated emotion recognition and its neural correlates in individuals with cocaine use disorder (CUD) parsed according to abstinence

Rationale and objectives The hippocampus, especially the CA1, CA3, and dentate gyrus (DG) subfields, is reported to be associated with post-traumatic stress disorder (PTSD) after trauma. However, neuroimaging studies of the associations between PTSD and hippocampal subfield volumes have failed to yield consistent findings. The aim of this study is to examine whether the dopamine D2 receptor (DRD2)

BACKGROUND Chronic inorganic arsenic (iAs) exposure induces deleterious effects on CNS including oxidative stress, cognitive deficits and altered brain neurochemistry. Little is known about the association between iAs and estrogen receptor expression in brain regions. AIMS AND OBJECTIVES Owing to the neuroprotective and estrogenic activities of resveratrol (RES), we examined the combined effects of

BACKGROUND Olanzapine (OLZ) is one of the most effective atypical antipsychotics but is associated with severe metabolic side effects, in which the gut microbiota plays an important role. Akkermansia muciniphila (A. muciniphila; Akk), a Gram-negative anaerobic bacterium in the intestine, can potentially improve metabolic syndrome. OBJECTIVE This study investigated the effect and underlying mechanisms

RATIONALE 4-Iodo-2,5-dimethoxy-N-(2-methoxybenzyl)phenethylamine (25I-NBOMe) is a potent serotonin 5-HT2A/2C receptor agonist with hallucinogenic activity. There is no data on the 25I-NBOMe effect on brain neurotransmission and animal performance after chronic administration. OBJECTIVES We examined the effect of a 7-day treatment with 25I-NBOMe (0.3 mg/kg/day) on neurotransmitters' release and rats'

RATIONALE Behavioral economics has shown that single-item demand indicators are promising for capturing crucial aspects of nicotine reinforcement. It is suggested that brief breakpoint measures perform comparably to full-length demand indices in characterizing nicotine dependence; however, there have been no thorough assessments of their validity in clinical settings. OBJECTIVES This study aimed to

Rationale Opioid use disorder (OUD) is highly comorbid with stress-related disorders, and stress can serve as a trigger for reinstatement of drug seeking. Glucocorticoid receptor (GR) antagonists such as mifepristone (RU-486) may be effective against stress-induced drug seeking. In the current study, PT150 (formerly ORG-34517), a more selective GR antagonist, was tested using two models of stress-induced

Rationale Gut microbiota plays an important role in host metabolism. Antipsychotic drugs can result in metabolic abnormalities. Probiotics may ameliorate the antipsychotic drug-induced metabolic abnormalities by regulating gut microbiota. Objective To determine whether Bifidobacterium intervention can ameliorate olanzapine-induced weight increase. Methods Enrolled patients were assigned to either the

Rationale Recently, it was found that cyclosomatostatin-induced catalepsy in middle-aged rats is accompanied by neuronal hypoactivation in the lateral entorhinal cortex (LEntCx); this hypoactivation was reversed by systemic administration of nicotine combined with diphenhydramine. These findings suggest the ability of nicotine to regulate catalepsy and the involvement of the LEntCx in this nicotine

A correction to this paper has been published: https://doi.org/10.1007/s00213-021-05859-y

Rationale and objective Environmental enrichment (EE) has been shown in old rats to improve learning and memory. Vitamin D (VitD) has also been shown to modulate age-related, cognitive dysfunction. As both EE and VitD could work to improve cognition via enhancement of neurotrophic factors, their effects might occlude one another. Therefore, a clinically relevant question is whether noted cognition-promoting

Rationale Preclinical studies demonstrate that the NK1 receptor is involved in opioid reinforcement and withdrawal expression. Few studies have examined the impact of treatment with NK1 antagonists on opioid response in humans. Objective To explore the potential for a selective NK1 antagonist, tradipitant, to attenuate the abuse liability and reinforcing and analgesic effects of oxycodone in opioid-experienced

Rationale Reducing nicotine content in cigarettes to ≤ 2.4 mg per g of tobacco [mg/g] reduces smoking behavior and toxicant exposure among adult daily smokers. However, cigarettes with similar nicotine content could support continued experimentation and smoking progression among young adults who smoke infrequently. Objectives This study evaluated the threshold for nicotine in cigarettes that produces

Rationale Most studies evaluating the safety and tolerability of intranasal oxytocin (OT) have not reported consistent adverse events (AEs), but they have largely focused on young men and single-dose administration. Thus, it is unclear whether these findings translate to older individuals and with longer administration periods. Objective Extending previous work, this study investigated the safety and

Rationale Studies on the attention-deficit/hyperactivity disorder (ADHD) have concluded that the disorder might be caused by a deficit in the inhibitory control of executive functions because of dopamine hypofunction. Recently, the intranasal route has emerged as an effective alternative means for sending dopamine directly to the brain. However, whether the treatment can ameliorate the deficits of

Rationale The prevalence of depression is ever-increasing throughout the population. However, available treatments are ineffective in around one-third of patients and there is a need for more effective and safer drugs. Objectives The antidepressant-like and procognitive effects of the “biased agonists” F15599 (also known as NLX-101) which preferentially targets postsynaptic 5-HT1A receptors and F13714

Rationale Arginine vasopressin (AVP) is a neuropeptide that modulates both physiological and emotional responses to threat. Until recently, drugs that target vasopressin receptors (V1a) in the human central nervous system were unavailable. The development of a novel V1a receptor antagonist, SRX246, permits the experimental validation of vasopressin’s role in the regulation of anxiety and fear in humans

The therapeutic potential of medical cannabis to treat a variety of conditions is becoming increasingly recognised. Globally, a large number of countries have now legalised cannabis for medical uses and a substantial number of patients are able to access their medications. Yet in the UK, where medical cannabis was legalised in November 2018, only a handful of NHS prescriptions have been written, meaning

Background Zebrafish are growing in use as a model for understanding drug dependence and addiction. Sensitization paradigms have been a useful tool in identifying mechanisms involved in drug-induced behavioral and neurological changes, but in zebrafish have tended to focus on locomotor, rather than cognitive, endpoints. Methods Here, we used a novel method, the FMP Y-maze, which measures continuous

Rationale In classical conditioning, sign-tracking reflects behavior directed toward a conditioned stimulus (CS) in expectation of a reward (unconditioned stimulus, US); in contrast, goal-tracking describes behavior directed toward the location of delivery of a US. As cues previously paired with drugs of abuse promote drug-seeking and drug-taking behavior in both animals and humans and thus contribute

Rationale Schizophrenia patients consistently show deficits in sensory-evoked broadband gamma oscillations and click-evoked entrainment at 40 Hz, called the 40-Hz auditory steady-state response (ASSR). Since such evoked oscillations depend on cortical N-methyl D-aspartic acid (NMDA)-mediated network activity, they can serve as pharmacodynamic biomarkers in the preclinical and clinical development of

Rationale Epigenetic regulation has been implicated in the incubation of drug craving (the time-dependent increase in drug seeking after prolonged withdrawal from drug self-administration). There is little information available on the role of microRNAs in incubation of heroin craving. Objective This study aimed to investigate the roles and mechanisms of miR-181a and methyl CpG binding protein 2 (MeCP2)

Objectives Long-term cannabis use has been associated with the appearance of psychotic symptoms and schizophrenia-like cognitive impairments; however these studies may be confounded by concomitant use of tobacco by cannabis users. We aimed to determine if previously observed cannabis-associated deficits in sensory gating would be seen in cannabis users with no history of tobacco use, as evidenced by