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Neurotherapeutics : the Journal of the... Oct 2020Tardive syndrome (TS) is an iatrogenic, often persistent movement disorder caused by drugs that block dopamine receptors. It has a broad phenotype including movement... (Review)
Review
Tardive syndrome (TS) is an iatrogenic, often persistent movement disorder caused by drugs that block dopamine receptors. It has a broad phenotype including movement (orobuccolingual stereotypy, dystonia, tics, and others) and nonmotor features (akathisia and pain). TS has garnered increased attention of late because of the Food and Drug Administration approval of the first therapeutic agents developed specifically for this purpose. This paper will begin with a discussion on pathogenesis, clinical features, and epidemiology. However, the main focus will be treatment options currently available for TS including a suggested algorithm based on current evidence. Recently, there have been significant advances in TS therapy, particularly with the development of 2 new vesicular monoamine transporter type 2 inhibitors for TS and with new data on the efficacy of deep brain stimulation. The discussion will start with switching antipsychotics and the use of clozapine monotherapy which, despite the lack of higher-level evidence, should be considered for the treatment of psychosis and TS. Anti-dyskinetic drugs are separated into 3 tiers: 1) vesicular monoamine transporter type 2 inhibitors, which have level A evidence, are approved for use in TS and are recommended first-choice agents; 2) drugs with lower level of evidence for efficacy including clonazepam, Ginkgo biloba, and amantadine; and 3) drugs that have the potential to be beneficial, but currently have insufficient evidence including levetiracetam, piracetam, vitamin B, melatonin, baclofen, propranolol, zolpidem, and zonisamide. Finally, the roles of botulinum toxin and surgical therapy will be examined. Current therapies, though improved, are symptomatic. Next steps should focus on the prevention and reversal of the pathogenic process.
Topics: Antioxidants; Antipsychotic Agents; Deep Brain Stimulation; Disease Management; Dopamine Antagonists; Humans; Neuroprotective Agents; Tardive Dyskinesia; Vesicular Monoamine Transport Proteins
PubMed: 32720245
DOI: 10.1007/s13311-020-00898-3 -
Annals of Medicine and Surgery (2012) Feb 2024Cardiovascular disease (CVD) is the most common cause of morbidity and mortality worldwide. Bromocriptine is a partial antagonist for D1 dopamine receptors while also... (Review)
Review
Cardiovascular disease (CVD) is the most common cause of morbidity and mortality worldwide. Bromocriptine is a partial antagonist for D1 dopamine receptors while also serving as a selective agonist on D2 dopamine receptors as a dopamine receptor agonist. Apart from prolactin inhibiting action, bromocriptine has some beneficial effects on the blood pressure, plasma norepinephrine levels and vascular resistance. Dopamine D2 receptor activation of bromocriptine is associated with the antihypertensive effect, which lowers blood pressure via inhibiting sympathetic nerve activity and Na/K ATPase activity. Plasma levels of the pro-inflammatory cytokines such as interleukin (IL)-1B and IL-18, chemokine CCL2/ MCP-1/, and the pro-inflammatory hormone prolactin, all of which are elevated and linked to accelerated cardiometabolic illness, were decreased because of bromocriptine therapy. The most common side effects of Bromocriptine use are dizziness, nausea, headache, vomiting and hypotension. Bromocriptine is mainly contraindicated in patients with syncope with hypotension, psychosis, and type I diabetes mellitus. The authors suggest that developing therapies directed to increase D2 receptor expression and function by drugs like Bromocriptine can provide practical and novelistic approaches to prevent and manage myocardial and renal injury in the cardiovascular disease patients.
PubMed: 38333315
DOI: 10.1097/MS9.0000000000001642 -
Neuropsychopharmacology : Official... May 2024The rewarding effects of stimulant drugs such as methylphenidate (MP) depend crucially on how fast they raise dopamine in the brain. Yet how the rate of drug-induced... (Randomized Controlled Trial)
Randomized Controlled Trial
The rewarding effects of stimulant drugs such as methylphenidate (MP) depend crucially on how fast they raise dopamine in the brain. Yet how the rate of drug-induced dopamine increases impacts brain network communication remains unresolved. We manipulated route of MP administration to generate fast versus slow dopamine increases. We hypothesized that fast versus slow dopamine increases would result in a differential pattern of global brain connectivity (GBC) in association with regional levels of dopamine D1 receptors, which are critical for drug reward. Twenty healthy adults received MP intravenously (0.5 mg/kg; fast dopamine increases) and orally (60 mg; slow dopamine increases) during simultaneous [C]raclopride PET-fMRI scans (double-blind, placebo-controlled). We tested how GBC was temporally associated with slow and fast dopamine increases on a minute-to-minute basis. Connectivity patterns were strikingly different for slow versus fast dopamine increases, and whole-brain spatial patterns were negatively correlated with one another (rho = -0.54, p < 0.001). GBC showed "fast>slow" associations in dorsal prefrontal cortex, insula, posterior thalamus and brainstem, caudate and precuneus; and "slow>fast" associations in ventral striatum, orbitofrontal cortex, and frontopolar cortex (p < 0.05). "Fast>slow" GBC patterns showed significant spatial correspondence with D1 receptor availability (estimated via normative maps of [C]SCH23390 binding; rho = 0.22, p < 0.05). Further, hippocampal GBC to fast dopamine increases was significantly negatively correlated with self-reported 'high' ratings to intravenous MP across individuals (r = -0.68, p = 0.015). Different routes of MP administration produce divergent patterns of brain connectivity. Fast dopamine increases are uniquely associated with connectivity patterns that have relevance for the subjective experience of drug reward.
Topics: Humans; Male; Adult; Female; Brain; Positron-Emission Tomography; Magnetic Resonance Imaging; Dopamine; Methylphenidate; Double-Blind Method; Young Adult; Raclopride; Central Nervous System Stimulants; Receptors, Dopamine D1; Neural Pathways; Dopamine Antagonists; Brain Mapping
PubMed: 38326458
DOI: 10.1038/s41386-024-01803-8 -
Biomedicine & Pharmacotherapy =... Jan 2022Dopamine (DA) is a crucial neurotransmitter that plays an important role in maintaining physiological function in human body. In the past, most studies focused on the... (Review)
Review
Dopamine (DA) is a crucial neurotransmitter that plays an important role in maintaining physiological function in human body. In the past, most studies focused on the relationship between the dopaminergic system and neurological-related diseases. However, it has been found recently that DA is an immunomodulatory mediator and many immune cells express dopamine receptors (DRs). Some immune cells can synthesize and secrete DA and then participate in regulating immune function. DRs agonists or antagonists can improve the dysfunction of immune system through classical G protein signaling pathways or other non-receptor-dependent pathways. This article will discuss the relationship between the dopaminergic system and the immune system. It will also review the use of DRs agonists or antagonists to treat chronic and acute inflammatory diseases and corresponding immunomodulatory mechanisms.
Topics: Central Nervous System; Dopamine; Dopamine Agonists; Dopamine Antagonists; Humans; Immune System; Immunologic Factors; Neurotransmitter Agents; Signal Transduction
PubMed: 34847478
DOI: 10.1016/j.biopha.2021.112458 -
Proceedings of the National Academy of... Mar 2022SignificanceDespite the identification of neural circuits and circulating hormones in olfactory regulation, the peripheral targets for olfactory modulation remain...
SignificanceDespite the identification of neural circuits and circulating hormones in olfactory regulation, the peripheral targets for olfactory modulation remain relatively unexplored. Here we show that dopamine D2 receptor (DRD2) is expressed in the cilia and somata of mature olfactory sensory neurons (OSNs), while nasal dopamine (DA) is mainly released from the sympathetic nerve terminals, which innervate the mouse olfactory mucosa (OM). We further demonstrate that DA-DRD2 signaling in the nose plays important roles in regulating olfactory function using genetic and pharmacological approaches. Moreover, the local DA synthesis in mouse OM is reduced during hunger, which contributes to starvation-induced olfactory enhancement. Altogether, we demonstrate that nasal DA and DRD2 receptor can serve as the potential peripheral targets for olfactory modulation.
Topics: Animals; Dopamine; Dopamine D2 Receptor Antagonists; Humans; Mice; Olfactory Receptor Neurons; Receptors, Dopamine D2; Signal Transduction; Smell
PubMed: 35263227
DOI: 10.1073/pnas.2118570119 -
PLoS Biology Jun 2020Dopamine guides behavior and learning through pleasure, according to classic understanding. Dopaminergic neurons are traditionally thought to signal positive or negative...
Dopamine guides behavior and learning through pleasure, according to classic understanding. Dopaminergic neurons are traditionally thought to signal positive or negative prediction errors (PEs) when reward expectations are, respectively, exceeded or not matched. These signed PEs are quite different from the unsigned PEs, which report surprise during sensory processing. But mounting theoretical accounts from the predictive processing framework postulate that dopamine, as a neuromodulator, could potentially regulate the postsynaptic gain of sensory neurons, thereby scaling unsigned PEs according to their expected precision or confidence. Despite ample modeling work, the physiological effects of dopamine on the processing of surprising sensory information are yet to be addressed experimentally. In this study, we tested how dopamine modulates midbrain processing of unexpected tones. We recorded extracellular responses from the rat inferior colliculus to oddball and cascade sequences, before, during, and after the microiontophoretic application of dopamine or eticlopride (a D2-like receptor antagonist). Results demonstrate that dopamine reduces the net neuronal responsiveness exclusively to unexpected sensory input without significantly altering the processing of expected input. We conclude that dopaminergic projections from the thalamic subparafascicular nucleus to the inferior colliculus could encode the expected precision of unsigned PEs, attenuating via D2-like receptors the postsynaptic gain of sensory inputs forwarded by the auditory midbrain neurons. This direct dopaminergic modulation of sensory PE signaling has profound implications for both the predictive coding framework and the understanding of dopamine function.
Topics: Acoustic Stimulation; Adaptation, Physiological; Animals; Cerebral Cortex; Dopamine; Female; Rats, Long-Evans; Salicylamides; Sound; Thalamus
PubMed: 32559190
DOI: 10.1371/journal.pbio.3000744 -
Neuropharmacology Jan 2020Emerging evidence suggest that appetite-regulating peptides modulate social behaviors. We here investigate whether the anorexigenic peptide neuromedin U (NMU) modulates...
Emerging evidence suggest that appetite-regulating peptides modulate social behaviors. We here investigate whether the anorexigenic peptide neuromedin U (NMU) modulates sexual behavior in male mice. However, instead of modulating sexual behaviors, NMU administered into the third ventricle increased self-grooming behavior. In addition, NMU-treatment increased self-grooming behavior when exposed to other mice or olfactory social-cues, but not when exposed to non-social environments. As the neuropeptide oxytocin is released during social investigation and exogenous oxytocin induces self-grooming, its role in NMU-induced self-grooming behavior was investigated. In line with our hypothesis, the oxytocin receptor antagonist inhibited NMU-induced self-grooming behavior in mice exposed to olfactory social-cues. Moreover, dopamine in the mesocorticolimbic system is known to be a key regulator of self-grooming behavior. In line with this, we proved that infusion of NMU into nucleus accumbens increased self-grooming behavior in mice confronted with an olfactory social-cue and that this behavior was inhibited by antagonism of dopamine D2, but not D1/D5, receptors. Moreover repeated NMU treatment enhanced ex vivo dopamine levels and decreased the expression of dopamine D2 receptors in nucleus accumbens in socially housed mice. On the other hand, the olfactory stimuli-dependent NMU-induced self-grooming was not affected by a corticotrophin-releasing hormone antagonist, and NMU-treatment did not influence repetitive behaviors in the marble burying test. In conclusion, our results suggest that NMU treatment and, social cues - potentially triggering oxytocin release - together induce excessive grooming behavior in male mice. The mesolimbic dopamine system, including accumbal dopamine D2 receptors, was identified as a crucial downstream mechanism.
Topics: Animals; Dopamine; Dopamine Antagonists; Dopamine D2 Receptor Antagonists; Grooming; Infusions, Intraventricular; Male; Mice; Neuropeptides; Nucleus Accumbens; Odorants; Oxytocin; Physical Stimulation; Receptors, Dopamine D1; Receptors, Dopamine D2; Receptors, Dopamine D5; Receptors, Oxytocin; Sexual Behavior, Animal; Smell; Social Behavior; Third Ventricle
PubMed: 31647973
DOI: 10.1016/j.neuropharm.2019.107818 -
Neuropharmacology Jun 2023Previous studies indicated that cotinine, the major metabolite of nicotine, supported intravenous self-administration and exhibited relapse-like drug-seeking behaviors...
Previous studies indicated that cotinine, the major metabolite of nicotine, supported intravenous self-administration and exhibited relapse-like drug-seeking behaviors in rats. Subsequent studies started to reveal an important role of the mesolimbic dopamine system in cotinine's effects. Passive administration of cotinine elevated extracellular dopamine levels in the nucleus accumbens (NAC) and the D1 receptor antagonist SCH23390 attenuated cotinine self-administration. The objective of the current study was to further investigate the role of mesolimbic dopamine system in mediating cotinine's effects in male rats. Conventional microdialysis was conducted to examine NAC dopamine changes during active self-administration. Quantitative microdialysis and Western blot were used to determine cotinine-induced neuroadaptations within the NAC. Behavioral pharmacology was performed to investigate potential involvement of D2-like receptors in cotinine self-administration and relapse-like behaviors. NAC extracellular dopamine levels increased during active self-administration of cotinine and nicotine with less robust increase during cotinine self-administration. Repeated subcutaneous injections of cotinine reduced basal extracellular dopamine concentrations without altering dopamine reuptake in the NAC. Chronic self-administration of cotinine led to reduced protein expression of D2 receptors within the core but not shell subregion of the NAC, but did not change either D1 receptors or tyrosine hydroxylase in either subregion. On the other hand, chronic nicotine self-administration had no significant effect on any of these proteins. Systemic administration of eticlopride, a D2-like receptor antagonist attenuated both cotinine self-administration and cue-induced reinstatement of cotinine seeking. These results further support the hypothesis that the mesolimbic dopamine transmission plays a critical role in mediating reinforcing effects of cotinine.
Topics: Rats; Male; Animals; Dopamine; Dopamine Antagonists; Cotinine; Nicotine; Receptors, Dopamine D2; Receptors, Dopamine D1; Nucleus Accumbens; Self Administration
PubMed: 36914092
DOI: 10.1016/j.neuropharm.2023.109495 -
International Journal of Molecular... Feb 2023Several theories have been proposed to explain the mechanisms of substance use in schizophrenia. Brain neurons pose a potential to provide novel insights into the...
Several theories have been proposed to explain the mechanisms of substance use in schizophrenia. Brain neurons pose a potential to provide novel insights into the association between opioid addiction, withdrawal, and schizophrenia. Thus, we exposed zebrafish larvae at 2 days post-fertilization (dpf) to domperidone (DPM) and morphine, followed by morphine withdrawal. Drug-induced locomotion and social preference were assessed, while the level of dopamine and the number of dopaminergic neurons were quantified. In the brain tissue, the expression levels of genes associated with schizophrenia were measured. The effects of DMP and morphine were compared to vehicle control and MK-801, a positive control to mimic schizophrenia. Gene expression analysis revealed that , , , , and th1 were up-regulated after 10 days of exposure to DMP and morphine, while was down-regulated. These two drugs also increased the number of positive dopaminergic neurons and the total dopamine level but reduced the locomotion and social preference. The termination of morphine exposure led to the up-regulation of , , and during the withdrawal phase. Our integrated data implicate that the dopamine system plays a key role in the deficits in social behavior and locomotion that are common in the schizophrenia-like symptoms and opioid dependence.
Topics: Animals; Calcium Channels; Dopamine; Dopaminergic Neurons; Morphine; Opioid-Related Disorders; Schizophrenia; Zebrafish; Domperidone; Dopamine Antagonists; Locomotion; Metabolic Networks and Pathways
PubMed: 36835497
DOI: 10.3390/ijms24044088 -
Comparative Biochemistry and... Oct 2022Chelonoidis carbonaria aortic rings present endothelium-derived release of dopamine, noradrenaline, adrenaline and 6-nitrodopamine (6-ND). Here it was investigated...
Chelonoidis carbonaria aortic rings present endothelium-derived release of dopamine, noradrenaline, adrenaline and 6-nitrodopamine (6-ND). Here it was investigated whether 6-ND release is coupled to nitric oxide (NO) synthesis and its action on the vascular smooth muscle reactivity. Basal release of 6-ND from aortic rings in the absence and presence of the NO synthesis inhibitor L-NAME was quantified by LC-MS-MS. Aortic rings were suspended vertically between two metal hooks in 10-mL organ baths containing Krebs-Henseleit's solution and attached to isometric transducers. The tissues were allowed to equilibrate for 1 h before starting the experiments. The release of 6-ND was significantly reduced by previous incubation with L-NAME. 6-ND (up to 300 μM) had no contractile activity in the aortic rings. 6-ND (1, 3 and 10 μM) produced significant rightward shifts of the concentration-response curves to dopamine in endothelium-intact (pA 6.09) and L-NAME pre-treated endothelium-intact (pA 7.06) aortic rings. Contractions induced by noradrenaline and adrenaline were not affected by pre-incubation with 6-ND. The EFS (16 Hz)-induced aortic contractions were significantly inhibited by incubation with 6-ND (10 μM). In the thromboxane A mimetic U-46619 (30 nM) pre-contracted endothelium intact aortic rings, 6-ND (1 nM-1 μM) and the dopamine D-receptor antagonist haloperidol (1 nM-1 μM) induced concentration-dependent relaxations. The relaxations were not present in endothelium-removed aortic rings but they were not affected by incubation with L-NAME in endothelium-intact aortic rings. The results indicate that the synthesis of this novel catecholamine in Chelonoidis carbonaria aortic rings is coupled to NO release and that 6-ND acts as a highly selective dopamine D-like receptor antagonist.
Topics: Animals; Aorta; Aorta, Thoracic; Dopamine; Dopamine Antagonists; Epinephrine; NG-Nitroarginine Methyl Ester; Nitric Oxide; Norepinephrine; Turtles
PubMed: 35793735
DOI: 10.1016/j.cbpc.2022.109403