Dopamine Neurotransmission Research Articles

Acute stimulation of PBMCs drives switch from dopamine-induced anti- to proinflammatory phenotype of monocytes only in women

Several studies report an impact of the neurotransmitter dopamine (DA) on human immune cells, with effects dependent on the immune cell type addressed and their activation status. Another contributing factor appears to be sex, as sex-specific differences in the dopaminergic pathway are described in the neurological context as well as in autoimmune diseases. However, a deeper understanding of these differences in peripheral immune cells remains limited. In this study, we investigated the effects of dopaminergic stimulation on activation and cytokine secretion of peripheral blood mononuclear cells from women and men using flow cytometry, ELISA, and multiplex assays. We found a B cell-driven downregulation in cytokine secretion of monocytes exclusively from women under physiological conditions in vitro. Moreover, B cells from men showed higher dopamine receptor (DR) expression, which was shown to be further increased by sex hormones only in men. In monocytes from women, an acute inflammatory stimulus via CpG combined with dopaminergic stimulation caused a switch to a proinflammatory phenotype, which was less pronounced in men. These novel findings in sex-specific responses to dopaminergic stimulation are crucial for understanding DA’s function in the healthy and activated immune system and provide evidence to treat DA-related pathologies in a sex-specific manner.

Focused Ultrasound Modulates Dopamine in a Mesolimbic Reward Circuit.

Dopamine is a neurotransmitter that plays a significant role in reward and motivation. Dysfunction in the mesolimbic dopamine pathway has been linked to a variety of psychiatric disorders, including addiction. Low-intensity focused ultrasound (LIFU) has demonstrated effects on brain activity, but how LIFU affects dopamine neurotransmission is not known. Here, we applied three different intensities (6.5, 13, and 26 W/cm2 ISPPA) of 2-min LIFU to the prelimbic cortex (PLC) and measured dopamine in the nucleus accumbens (NAc) core using fast-scan cyclic voltammetry. Two minutes of LIFU sonication at 13 W/cm2 to the PLC significantly reduced dopamine release by ~50% for up to 2 h. However, double the intensity (26 W/cm2) resulted in less inhibition (~30%), and half the intensity (6.5 W/cm2) did not result in any inhibition of dopamine. Anatomical controls applying LIFU to the primary somatosensory cortex did not change NAc core dopamine, and applying LIFU to the PLC did not affect dopamine release in the caudate or NAc shell. Histological evaluations showed no evidence of cell damage or death. Modeling temperature rise demonstrates a maximum temperature change of 0.5°C with 13 W/cm2, suggesting that modulation is not due to thermal mechanisms. These studies show that LIFU at a moderate intensity provides a noninvasive, high spatial resolution means to modulate specific mesolimbic circuits that could be used in future studies to target and repair pathways that are dysfunctional in addiction and other psychiatric diseases.

Altered resting-state cerebral blood flow and its relationship with molecular architecture in tremor dominant Parkinson's disease.

The resting-state cerebral blood flow (CBF) alterations in Parkinson's disease (PD) patients and tremor-dominant (TD) subtype have been explored. However, the underlying molecular architecture correlated with the altered CBF remains unknown. In total, 90 PD patients including 41 TD subtype, and 90 healthy controls (HC) underwent arterial spin labelling magnetic resonance image. The altered CBF were derived by a voxel-wised two sample t-test compare and spatial correlated with serotonin, dopamine, γ-aminobutyric acid, opioid, noradrenaline, N-methyl-D-aspartic acid, acetylcholine and glutamate neurotransmitter density maps. Compared to HC, PD patients exhibited decreased CBF in left caudate/putamen, increased CBF in bilateral supplementary motor area (SMA). Moreover, the CBF of SMA showed a positive correlation with disease severity. The altered CBF in PD patients were significantly associated with spatial distribution of serotonin 5-hydroxytryptamine receptor, dopamine receptor, and noradrenaline transporter. Compared to non-tremor-dominant subtype, the TD subtype exhibited decreased CBF in left calcarine/cuneus, increased CBF in left middle frontal gyrus and bilateral superior frontal gyrus. The altered CBF in the TD subtype were significantly associated with spatial distribution of serotonin 5-hydroxytryptamine, dopamine, glutamate, and opioid receptors. Besides dopamine, perfusion alterations in SMA of PD patients were more probably correlated with serotonin and noradrenaline. Perfusion alterations of the TD subtype were related to dopamine, serotonin, other excitatory neurotransmitters such as glutamate and opioid, which may provide novel insights into pathophysiological processes and guide new therapeutic targets.

Dopamine genetic risk scores and psychiatric symptoms: Interacting risk factors for impulse control behaviours in de novo Parkinson's disease.

Up to 45% of patients with Parkinson's disease (PD) experience impulse control disorders (ICDs), characterized by a loss of voluntary control over impulses, drives or temptations. This study aimed to investigate whether previously identified genetic and psychiatric risk factors interact towards the development of ICDs in PD. A total of 278 de novo PD patients (ICD-free at enrollment) were selected from the Parkinson's Progression Markers Initiative database. ICD presence at baseline and yearly follow-up assessments were evaluated via the Questionnaire for Impulsive-Compulsive Disorders. Symptoms of anxiety and depression at baseline were measured via the State-Trait-Anxiety Inventory and Geriatric Depression Scale, respectively. Furthermore, an individual dopamine genetic risk score was calculated according to polymorphisms in genes coding for dopamine (D1, D2 and D3 receptors and catechol-O-methyltransferase), with higher scores reflecting higher central dopamine neurotransmission. In total, 146 participants (47.5%) developed an ICD with an average onset time of 36 months (range 3-96) from baseline. Results from a Cox proportional hazards model showed a trait anxiety × genetics interaction, suggesting that individuals with both higher baseline trait anxiety scores and higher dopamine genetic risk scores were at increased risk of ICD development. This interaction remained significant after controlling for age, sex and motor symptom severity. Our findings suggest that genetic and psychiatric predictors of impulsivity in PD interact and jointly yield increased ICD risk during the course of the disorder. This implies that early screening of anxiety symptoms in combination with genotyping can be useful to identify those at risk for ICD.

Case Series of Anesthetic Management of Gene Therapy in Children With Aromatic L-Amino Acid Decarboxylase Deficiency.

Aromatic L-amino acid decarboxylase (AADC) deficiency is a rare life-threatening inborn error of neurotransmitter biosynthesis. It is characterized by deficient biosynthesis of neurotransmitters dopamine and serotonin, leading to catecholamines deficiency and sympathetic deprivation, while the parasympathetic system remains functional. Since 2012, gene therapy has led to clinical improvements in symptoms and motor function with a severe phenotype. General anesthesia of children with AADC deficiency is challenging. Describe prolonged anesthesia management of children with aromatic L-amino acid decarboxylase deficiency undergoing stereotactically guided gene therapy. Prospective reporting of epidemiologic and anesthetics data of four children consecutively undergoing magnetic resonance-guided direct delivery of an AADC vector for gene therapy under general anesthesia. General anesthesia was initiated with sevoflurane and ketamine and rocuronium was the neuromuscular blocking agent of choice throughout the procedures. Intraoperative hemodynamic monitoring included an arterial line. All children required low doses of diluted norepinephrine during the intraoperative period. No dysautomic episodes as well as no episode of severe hypotension and no severe hypoglycemia were reported throughout the procedures. Vasopressor support was discontinued for all children at the end of the procedures. Moreover, no peroperative and postoperative effects secondary to AADC vector injection were noted. Using an anesthetic plan based on atropine, ketamine, sevoflurane, and a titrated infusion of norepinephrine, prolonged anesthesia appeared to be safe and reproductible in this population.

Trace amine signaling in zebrafish models: CNS pharmacology, behavioral regulation and translational relevance.

Tyramine, β-phenylethylamine, octopamine and other trace amines are endogenous substances recently recognized as important novel neurotransmitters in the brain. Trace amines act via multiple selective trace amine-associated receptors (TAARs) of the G protein-coupled receptor family. TAARs are expressed in various brain regions and modulate neurotransmission, neuronal excitability, adult neurogenesis, cognition, mood, locomotor activity and olfaction. Disrupted trace amine circuits have been implicated in various clinical neuropsychiatric disorders, including schizophrenia, Parkinson's disease, addiction, depression and anxiety. Dysregulated TAAR signaling has been linked in rodents to altered dopamine and serotonin neurotransmission, known to be associated with these psychiatric conditions. Complementing rodent genetic and pharmacological evidence, zebrafish (Danio rerio) are rapidly becoming a novel powerful model system in translational neuropharmacology research. Here, we review trace amine/TAAR neurobiology in zebrafish and discuss their developing translational utility as pharmacological and genetic models for unraveling the role of trace amines in CNS processes and brain disorders.

The effects of haloperidol on motor vigour and movement fusion during sequential reaching.

Reward is a powerful tool to enhance human motor behaviour with previous research showing that during a sequential reaching movement, a monetary incentive leads to increased speed of each movement (motor vigour effect), whilst reward-based performance feedback increases the speed of transition between movements (movement fusion effect). The neurotransmitter dopamine plays a central role in the processing of reward signals and has been implicated to modulate motor vigour and regulate movement fusion. However, in humans, it is unclear if the same dopaminergic mechanism underlies both processes. To address this, we used a complex sequential reaching task in which rewards were based on movement times (MT). Crucially, MTs could be reduced via: 1) enhanced speed of individual movements (motor vigour effect) and/or 2) enhanced speed of transition between movements (movement fusion effect). 95 participants were randomly assigned to a reward or no reward group and were given either 2.5mg of the dopamine antagonist haloperidol or a placebo (control group). An independent decision-making task performed prior to the main experiment suggested that haloperidol was active during the sequential reaching task (positive control). We did not find evidence that haloperidol affected the facilitatory effects of reward on movement fusion. However, we found that haloperidol negated the reward-based effects on motor vigour. Therefore, our results suggest that a D2-antagonist differentially influences reward-based effects on movement vigour and movement fusion, indicating that the dopaminergic mechanisms underlying these two processes may be distinct.

Pharmacological Modulation of Dopamine Receptors Reveals Distinct Brain-Wide Networks Associated with Learning and Motivation in Nonhuman Primates.

The neurotransmitter dopamine (DA) has a multifaceted role in healthy and disordered brains through its action on multiple subtypes of dopaminergic receptors. How the modulation of these receptors influences learning and motivation by altering intrinsic brain-wide networks remains unclear. Here, we performed parallel behavioral and resting-state functional MRI experiments after administration of two different DA receptor antagonists in male and female macaque monkeys. Systemic administration of SCH-23390 (D1 antagonist) slowed probabilistic learning when subjects had to learn new stimulus-reward associations and diminished functional connectivity (FC) in corticocortical and frontostriatal connections. In contrast, haloperidol (D2 antagonist) improved learning and broadly enhanced FC in cortical connections. Further comparisons between the effect of SCH-23390/haloperidol on behavioral and resting-state FC revealed specific cortical and subcortical networks associated with the cognitive and motivational effects of DA manipulation, respectively. Thus, we reveal distinct brain-wide networks that are associated with the dopaminergic control of learning and motivation via DA receptors.

Tardive Dyskinesia: A Complicated Iatrogenic Movement Condition-An Updated Overview of Diagnosis, Management, and Pharmacological Treatment

Background: Tardive dyskinesia (TD) is a complex iatrogenic movement disorder resulting from prolonged dopamine receptor antagonism. It presents as involuntary abnormal movements such as akathisia, dystonia, and buccolingual stereotypy, predominantly affecting individuals on long-term antipsychotics. Despite the cessation of the causative medication, symptoms often persist, complicating management. Aim: This review provides an updated overview of the diagnosis, management, and pharmacological treatment options for TD, emphasizing its multifaceted nature and the challenges it presents. Methods: The article synthesizes current evidence on TD's etiology, pathophysiology, clinical presentation, and treatment strategies. Key diagnostic tools, including the Abnormal Involuntary Movement Scale (AIMS), and therapeutic approaches such as vesicular monoamine transporter (VMAT2) inhibitors, are discussed. Results: The etiology of TD is linked to first- and second-generation antipsychotics, with the former posing a greater risk. Pathophysiological insights highlight dopamine receptor hypersensitivity, oxidative stress, and neurotransmitter interactions as pivotal contributors. Diagnosis is reliant on symptom persistence post-medication exposure. While treatment options remain limited, valbenazine and deutetrabenazine show efficacy. Preventative measures, including cautious prescribing and regular monitoring, are crucial. Conclusion: TD remains a challenging condition with significant implications for affected individuals. Comprehensive evaluation and targeted therapies are essential for effective management. Advances in VMAT2 inhibitors offer promise, but prevention through judicious medication use is paramount.

Cholinergic regulation of decision making under risk of punishment.

The ability to choose between options that differ in their risks and rewards depends on brain regions within the mesocorticolimbic circuit and regulation of their activity by neurotransmitter systems. Dopamine neurotransmission in particular plays a critical role in modulating such risk-taking behavior; however, the contribution of other major modulatory neurotransmitters, such as acetylcholine, is not as well-defined, especially for decision making in which the risk associated with more rewarding outcomes involves adverse consequences. Consequently, the goal of the current experiments was to examine how cholinergic signaling influences decision making involving risk of explicit punishment. Male and female rats were trained in a decision-making task in which they chose between a small safe food reward and a larger food reward accompanied by a risk of footshock punishment. After training in this task, the effects of nicotinic and muscarinic agonists and antagonists on risk-taking performance were evaluated. Neither nicotine, a nicotinic receptor agonist, nor mecamylamine, a nicotinic receptor antagonist, affected preference for the risky lever, although mecamylamine did alter latencies to press the risky lever and the percentage of omissions. The muscarinic receptor agonist oxotremorine decreased preference for the large, risky lever; similar effects on behavior were observed with the administration of the muscarinic receptor antagonist scopolamine. Control experiments were therefore conducted in which these same muscarinic receptor ligands were administered prior to testing in a reward discrimination task. These experiments revealed that the effects of oxotremorine and scopolamine on risk taking may be due to altered motivational processes rather than to changes in sensitivity to risk of punishment. Importantly, there were no sex differences in the effects of cholinergic manipulations on preference for the large, risky lever. Collectively, these findings suggest that in both males and females, cholinergic signaling via muscarinic receptors is involved in decision making involving risk of explicit punishment, with a specific role in modulating sensitivity to differences in reward magnitude. Future studies will expand upon this work by exploring whether targeting cholinergic receptors has therapeutic potential for psychiatric conditions in which risk taking is pathologically altered.

Potential therapeutic effect of teneligliptin on unpredictable chronic mild stress-induced depression in mice: targeting the role of AMP-activated protein kinase signaling pathway

Background Depression is a widespread and complex mental disorder that is challenging to treat. The unpredictable chronic mild stress (UCMS) model, based on stress diathesis, is used to study depression because antidepressants often reverse its effects, providing predictive validity. However, the mechanisms behind UCMS are not fully understood. AMP-activated protein kinase (AMPK) is essential for regulating neuronal energy metabolism, and disruptions in its activation can impair brain function and synaptic integrity. Teneligliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor with anti-inflammatory, antioxidant, autophagy-modulating, and antiapoptotic properties, has not been studied for its potential to activate AMPK by inhibiting DPP-4, stimulating glucagon-like peptide-1, and decreasing the mammalian target of rapamycin pathway, which may enhance neuroprotection and neurogenesis. This study is the first to show teneligliptin’s potential therapeutic effect on UCMS-induced depression in mice by targeting the AMPK signaling pathway. Objective The current study was performed to assess the behavioral, oxidative stress biomarkers, neurotransmitter assay, and histopathology of the brain in UCMS-induced depression in mice. Materials and methods Mice were divided into five groups: group I (normal control, received saline), group II (UCMS model with 1 week of stress), group III (UCMS+fluoxetine 10 mg/kg daily for 4 weeks), and groups IV and V (UCMS+teneligliptin 30 mg/kg and 60 mg/kg, respectively, for 4 weeks). Body weight, forced swim test, tail suspension, locomotor activity, oxidative biomarkers (malondialdehyde, reduced glutathione, superoxide dismutase, nitrite levels), neurotransmitters (dopamine, serotonin), and brain histopathology were assessed to evaluate antidepressant activity. Results and conclusion Mice treated with teneligliptin (30 and 60 mg/kg) in the UCMS model showed significant weight loss compared with the disease group. They also exhibited reduced immobility in forced swim and tail suspension tests and increased locomotor activity. Significant changes were noted in oxidative stress biomarkers and neurotransmitters (dopamine, serotonin), with improved histopathological conditions. In conclusion, teneligliptin improved behavioral and antidepressant effects by reducing oxidative stress and increasing dopamine and serotonin levels. As a DPP-4 inhibitor, it may activate AMPK in the brain, lower DPP-4 enzyme levels, and enhance glucagon-like peptide-1-R and mammalian target of rapamycin, potentially promoting neurogenesis and neuroprotection, thus being beneficial for depression treatment.

Midbrain dopamine drives splenic immunity through a brain-to-body circuit.

Midbrain dopamine neurons are well-known to shape central nervous system function, yet there is growing evidence for their influence on the peripheral immune systems. Here we demonstrate that midbrain dopamine neurons form a circuit to the spleen via a multisynaptic pathway from the dorsal vagal complex (DVC) through the celiac ganglion. Midbrain dopamine neurons modulate the activity of D1-like and D2-like dopamine receptor-expressing DVC neurons. In vivo activation of midbrain dopamine neurons induced dopamine release in the DVC and increased immediate early gene expression in both the DVC and celiac ganglion, indicating enhanced neuronal activity. Activation of this midbrain-to-spleen circuit reduced spleen weight and decreased naïve CD4 + T-cell populations without affecting total T-cell numbers. These findings unveil a functional midbrain-DVC-celiac ganglion-spleen pathway, through which midbrain dopamine neurons modulate splenic immunity. These novel insights into the neural regulation of the immune system have important implications for diseases involving altered dopamine neurotransmission and highlight potential targets for immunotherapeutic interventions.

Effect of sleep disturbances on depression

This paper explores the relationship between sleep disorders and depression, highlighting the complex interplay between various influencing factors. This article will analyze the influence of sleep disorders on depression from three aspects: pathological mechanisms, different age groups, and lifestyle factors. The analysis began with pathological mechanisms, particularly the role of neurotransmitter systems, including histamine, norepinephrine, dopamine, and serotonin, all of which significantly regulate sleep and mood states. Dysregulation of these neurotransmitters can exacerbate sleep disturbances, thereby increasing the risk of depression. The researchers also examined the age factor and found that sleep deprivation in adolescents impaired emotion regulation and significantly increased the risk of depression. In contrast, older adults with sleep disorders were three times more likely to develop depression over time. In addition, lifestyle factors such as dietary habits, exercise, and use of electronic devices were explored. A balanced diet and regular physical activity have been shown to improve sleep quality and reduce depressive symptoms. In contrast, the use of electronic devices, especially at bedtime, is associated with poorer sleep outcomes and a higher risk for depression owing to the damaging effect of blue light on melatonin secretion.

Paraxanthine enhances memory and neuroplasticity more than caffeine in rats

Paraxanthine (PXN) is the main metabolite of caffeine (CAF). PXN supplementation has been shown to increase measures of cognition, memory, reasoning, response time, and sustained attention; however, no preclinical study has compared the effects of PXN with those of CAF. The aim of this study was to compare the effects of PXN and CAF on memory and related biomarkers in rats. The effects of two different doses of PXN (PXN LOW, PXN HIGH), CAF (CAF HIGH), and a control group on cognition (escape latency in the Morris water maze test), neurotransmitters (acetylcholine, dopamine, and gamma-aminobutyric acid), and neurochemicals (BDNF, catalase, glutathione, and cyclic GMP) were analyzed from whole brain samples in young (8 weeks old) and aged (16 months old) rats. Compared to the control group, escape latency improved in PXN LOW, PXN HIGH, and CAF HIGH (all P < 0.05) in young animals, and in PXN HIGH and CAF HIGH in older animals (P < 0.001). PXN HIGH improved escape latency compared to CAF HIGH in both young (P < 0.001) and old animals (P = 0.003). BDNF levels increased in PXN LOW, PXN HIGH, and CAF HIGH (all P < 0.001), with PXN HIGH increasing BDNF to a greater extent compared to CAF HIGH (P = 0.03). PXN HIGH also significantly increased BDNF levels compared to PXN LOW (P < 0.001). All other neurotransmitters and neurochemicals significantly increased in the PXN HIGH and CAF HIGH groups compared to the control. In conclusion, PXN showed greater improvements in cognition and BDNF levels compared to CAF, further substantiating PXN as a nootropic with greater benefits compared to CAF.

How antipsychotics work in schizophrenia: a primer on mechanisms.

Antipsychotics effective for schizophrenia approved prior to 2024 shared the common mechanism of postsynaptic dopamine D2 receptor antagonism or partial agonism. Positive psychosis symptoms correlate with excessive presynaptic dopamine turnover and release, yet this postsynaptic mechanism improved positive symptoms only in some patients, and with concomitant risk for off-target motor and endocrine adverse effects; moreover, these agents showed no benefit for negative symptoms and cognitive dysfunction. The sole exception was data supporting cariprazine's superiority to risperidone for negative symptoms. The muscarinic M1/M4 agonist xanomeline was approved in September 2024 and represents the first of a new antipsychotic class. This novel mechanism improves positive symptoms by reducing presynaptic dopamine release. Xanomeline also lacks any D2 receptor affinity and is not associated with motor or endocrine side effects. Of importance, xanomeline treated patients with higher baseline levels of cognitive dysfunction in clinical trials data saw cognitive improvement, a finding likely related to stimulation of muscarinic M1 receptors. Treatment resistance is seen in one-third of schizophrenia patients. These individuals do not have dopamine dysfunction underlying their positive symptoms, and therefore show limited response to antipsychotics that target dopamine neurotransmission. Clozapine remains the only medication with proven efficacy for resistant schizophrenia, and with unique benefits for persistent impulsive aggression and suicidality. New molecules are being studied to address the array of positive, negative and cognitive symptoms of schizophrenia; however, until their approval, clinicians must be familiar with currently available agents and be adept at prescribing clozapine.

Dysregulated acetylcholine-mediated dopamine neurotransmission in the eIF4E Tg mouse model of autism spectrum disorders

Autism spectrum disorder (ASD) consists of diverse neurodevelopmental conditions where core behavioral symptoms are critical for diagnosis. Altered dopamine (DA) neurotransmission in the striatum has been suggested to contribute to the behavioral features of ASD. Here, we examine DA neurotransmission in a mouse model of ASD characterized by elevated expression of eukaryotic initiation factor 4E (eIF4E), a key regulator of cap-dependent translation, using a comprehensive approach that encompasses genetics, behavior, synaptic physiology, and imaging. The results indicate that increased eIF4E expression leads to behavioral inflexibility and impaired striatal DA release. The loss of normal DA neurotransmission is due to a defect in nicotinic receptor signaling that regulates calcium dynamics in dopaminergic axons. These findings provide a mechanistic understanding of ASD symptoms and offer a foundation for targeted therapeutic interventions by revealing the intricate interplay between eIF4E, DA neurotransmission, and behavioral flexibility.

Successful treatment of psychosis with metyrosine in a young adult with velocardiofacial syndrome: a case report

Velocardiofacial syndrome (VCFS) has many psychiatric manifestations along with multiple physical findings such as developmental delay, cardiac abnormalities, palatal anomalies, and immune deficiency. As many as 41% of individuals with VCFS have experienced a psychotic disorder– a disabling and distressing condition. One of the missing genes in the syndrome is catechol-O-methyltransferase (COMT) that is involved in dopamine metabolism and neurotransmission, and one possible implication of this haploinsufficiency is higher dopamine levels in the prefrontal cortex. We present a case of VCFS- associated psychosis that was unresponsive to traditional antipsychotic agent trials but responded to a trial of metyrosine, an older antihypertensive medication that inhibits catecholamine synthesis. Since the initiation of metyrosine, the patient has had no psychiatric hospitalizations in three years, a distinct and dramatic difference from the two years prior to the initiation of the medication. Metyrosine is not a first line treatment for VCFS-related psychosis. Prior to its initiation, traditional antipsychotics should be tried and clozapine would be an option for treatment-resistant cases.

Elevating levels of the endocannabinoid 2-arachidonoylglycerol blunts opioid reward but not analgesia.

Converging findings have established that the endocannabinoid (eCB) system serves as a possible target for the development of new treatments as a complement to opioid-based treatments. Here, we show in male and female mice that enhancing levels of the eCB, 2-arachidonoylglycerol (2-AG), through pharmacological inhibition of its catabolic enzyme, monoacylglycerol lipase (MAGL), either systemically or in the ventral tegmental area (VTA) with JZL184, leads to a substantial attenuation of the rewarding effects of opioids in mice using conditioned place preference and self-administration paradigms, without altering their analgesic properties. These effects are driven by cannabinoid receptor 1 (CB1R) within the VTA, as VTA CB1R conditional knockout counteracts JZL184's effects. Using fiber photometry with fluorescent sensors for calcium and dopamine (DA), we find that enhancing 2-AG levels diminishes opioid reward-related nucleus accumbens (NAc) activity and DA neurotransmission. Together, these findings reveal that 2-AG diminishes the rewarding properties of opioids and provides a potential adjunctive therapeutic strategy for opioid-related analgesic treatments.

Dysregulation of dopamine neurotransmission in drug addicts: implications for criminal behavior and corrective interventions.

Drug addiction often correlates with criminal behavior. When investigating criminal behavior among individuals grappling with drug addiction, it becomes crucial to scrutinize the influence of dopamine. Substances such as heroin, morphine, methamphetamine and other drugs can cause abnormal dopamine secretion when people are addicted to them, which promotes changes in the brain's reward circuit and emotional balance, thereby increasing susceptibility to criminal behavior. The pivotal role of dopamine within the reward pathway and its regulatory function in emotional processes exert profound influence on behavior following drug simulation. These influences are primarily manifested by three distinct attributes: a singular criminal motive and objective, lack of moral sense, and impulsive decision-making processes. Drawing upon the distinctive dopaminergic dynamics inherent in individuals afflicted by drug addiction, this study advocates for targeted corrective interventions. The preventive paradigm encompasses the cultivation of supportive community environments, the establishment of comprehensive databases, and providing legal education and protection, among other initiatives. In terms of treatment, along with judicial sanctions and protections, exercise regimens and psychotherapeutic interventions are advocated. The corrective endeavor necessitates a synergistic integration of community-based and legalistic frameworks. The objective is to furnish guiding principles for tackling criminal behavior precipitated by aberrant dopamine secretion, underpinned by a scientifically informed approach.

Boost Your Mood with Mucuna pruriens

Mucuna pruriens, a tropical legume, has garnered attention for its therapeutic potential, particularly due to its high L-DOPA content, a precursor to the neurotransmitter dopamine. This review paper synthesizes current research on the pharmacological properties of Mucuna pruriens, emphasizing its application in treating neurological disorders such as Parkinson’s disease. Traditional uses in various indigenous medicine systems have been validated through modern scientific methods, demonstrating significant anti-parkinsonian potential without the common side effects associated with synthetic L-DOPA. The analysis extends to the agronomic practices essential for its cultivation, which highlights the plant's dual role in sustainable agriculture and therapeutic applications. This review also addresses the critical aspects of toxicity and safety profiles, elaborating on the appropriate dosages and preparations to mitigate side effects commonly associated with natural products. Furthermore, the economic implications of Mucuna pruriens in the pharmaceutical industry are discussed, underlining its potential as a cost-effective treatment option. Comparative studies with other natural sources of L-DOPA offer a comprehensive overview of its advantages over synthetic alternatives, providing insights into its higher efficacy and lower toxicity. The review concludes with suggestions for future research directions, particularly in genetic variability, which could pave the way for enhanced therapeutic profiles tailored to individual needs. This paper aims to contribute to the broader understanding of Mucuna pruriens, encouraging further clinical and agronomic research to fully exploit its potential.