Результаты поиска

Dopamine: The Neuromodulator of Long-Term Synaptic Plasticity, Reward and Movement Control.

Dopamine (DA) is a key neurotransmitter involved in multiple physiological functions including motor control, modulation of affective and emotional states, reward mechanisms, reinforcement of behavior, and selected higher cognitive functions. Dysfunction in dopaminergic transmission is recognized as a core alteration in several devastating neurological and psychiatric disorders, including Parkinson's disease (PD), schizophrenia, bipolar disorder, attention deficit hyperactivity disorder (ADHD) and addiction. Here we will discuss the current insights on the role of DA in motor control and rewar…

Treatment-resistant schizophrenia characterised by dopamine supersensitivity psychosis and efficacy of asenapine.

Dopamine supersensitivity psychosis (DSP) frequently arises with long-term antipsychotic treatment and accounts for a significant proportion of treatment-resistant schizophrenia. The mechanism underlying DSP is thought to be a compensatory increase in dopamine receptor density in the striatum caused by long-term antipsychotic treatment. Previous animal studies have reported that antipsychotics increase serotonin 5-HT2A receptor density in the striatum and that 5-HT2A receptor blockers suppress dopamine-sensitive psychomotor activity, which may be linked to the pathophysiology of DSP. In this p…

Dopamine neurons gate the intersection of cocaine use, decision making, and impulsivity.

Gambling and substance use disorders are highly comorbid. Both clinical populations are impulsive and exhibit risky decision-making. Drug-associated cues have long been known to facilitate habitual drug-seeking, and the salient audiovisual cues embedded within modern gambling products may likewise encourage problem gambling. The dopamine neurons of the ventral tegmental area (VTA) are exquisitely sensitive to drugs of abuse, uncertain rewards, and reward-paired cues and may therefore be the common neural substrate mediating synergistic features of both disorders. To test this hypothesis, we fi…

Dopamine dysfunction in stimulant use disorders: mechanistic comparisons and implications for treatment.

Dopamine system deficiencies and associated behavioral phenotypes may be a critical barrier to success in treating stimulant use disorders. Similarities in dopamine dysfunction between cocaine and methamphetamine use disorder but also key differences may impact treatment efficacy and outcome. This review will first compare the epidemiology of cocaine and methamphetamine use disorder. A detailed account of the pharmacokinetic and pharmacodynamic properties associated with each drug will then be discussed, with an emphasis on effects on the dopamine system and associated signaling pathways. Last…

Synaptic Zn2+ potentiates the effects of cocaine on striatal dopamine neurotransmission and behavior.

Cocaine binds to the dopamine (DA) transporter (DAT) to regulate cocaine reward and seeking behavior. Zinc (Zn2+) also binds to the DAT, but the in vivo relevance of this interaction is unknown. We found that Zn2+ concentrations in postmortem brain (caudate) tissue from humans who died of cocaine overdose were significantly lower than in control subjects. Moreover, the level of striatal Zn2+ content in these subjects negatively correlated with plasma levels of benzoylecgonine, a cocaine metabolite indicative of recent use. In mice, repeated cocaine exposure increased synaptic Zn2+ concentratio…

Clinical and Dopamine Depletion Patterns in Hyposmia- and Dysautonomia-Dominant Parkinson's Disease.

BACKGROUND: Olfactory or autonomic dysfunction is one of the earliest prodromal symptoms of Parkinson's disease (PD). It has not been invest … inant and dysautonomia-dominant PD have different clinical characteristics and patterns of striatal dopamine depletion.

Свободное сотовое синтезирование дофамина и серотонина в двух шагах с очищенными ферментами.

Описывают синтез серотонина и дофамина с очищенными ферментами. Оба пути начинаются с субстрата аминокислоты и синтезируют нейротрансмиттер моноамина двумя энзиматическими шагами. Энцимы человека триптофановой гидроксилазы изоформы 2, Rattus Norvegicus tirosine гидроксилаза, хламидийная пневмония Cpn1046 и ароматическая аминокислота декарбоксилаза из дрософила меланогастера рекомбинированы, очищены и доказали свою функциональность in vitro. Гидроксилазы эффективно преобразуют L-DOPA (L-дигидрокси-фенилалин) и 5-HTP (5-гидрокриптофан) соответственно из L-стиросин и L-триптофана. Единственная ар

Совпадение в аннотации оригинала
The synthesis of serotonin and dopamine with purified enzymes is described. Both pathways start from an amino acid substrate and synthesize the monoamine neurotransmitter in two enzymatic steps. The enzymes human tryptophan hydroxylase isoform 2, Rattus norvegicus tyrosine hydroxylase, Chlamydia pneumoniae Cpn1046, and aromatic amino acid decarboxylase from …

Factors to Consider in the Selection of Dopamine Agonists for Older Persons with Parkinson's Disease.

Dopamine agonists (DAs) are frequently used in the management of Parkinson's disease (PD), a complex multisystem disorder influenced substantially by age-related factors. Over 80% of PD patients present after age 60 years and may have clinical features exacerbated by age-related comorbidities or decline in physiological compensatory mechanisms. Pharmacotherapy for motor symptoms in older persons is more likely to involve exclusive use of levodopa combined with a peripheral decarboxylase inhibitor throughout the course of the illness. Non-ergot DAs, such as pramipexole, rotigotine and ropinirol…

Expectation effects on brain dopamine responses to methylphenidate in cocaine use disorder.

The response to drugs of abuse is affected by expectation, which is modulated in part by dopamine (DA), which encodes for a reward prediction error. Here we assessed the effect of expectation on methylphenidate (MP)-induced striatal DA changes in 23 participants with an active cocaine use disorder (CUD) and 23 healthy controls (HC) using [11C]raclopride and PET both after placebo (PL) and after MP (0.5 mg/kg, i.v.). Brain dopamine D2 and D3 receptor availability (D2R: non-displaceable binding potential (BPND)) was measured under four conditions in randomized order: (1) expecting PL/receiving P…

The role of dopamine in eye growth responses to color and luminance flicker in chicks.

Stroboscopic luminance flicker has been found to prevent the increase in eye growth normally associated with form deprivation through the release of retinal dopamine. In this study, we sought to investigate whether dopamine plays a role in the decreased growth observed with 2 Hz sine-wave luminance flicker and increased growth with color flicker. Starting 5-7 days after hatching, chicks were exposed to 2 Hz sinusoidally modulated illumination (Mean: 680 lux) for 4 days and were otherwise in the dark. Chicks were exposed to color-modulated red and green (RG) light, to luminance modulated RGB co…

Microglial glutamate release evoked by α-synuclein aggregates is prevented by dopamine.

When activated, microglial cells have the potential not only to secrete typical proinflammatory mediators but also to release the neurotrans … NADPH oxidase activation. Of interest, the stimulation of glutamate release by αSa was abrogated by dopamine through an antioxidant effect requiring D1 dopamine receptor activation and PI3K inhibition. Altogether, present data suggest that the activation of microglial cells by αSa may possibly result in a toxic build-up of extracellular glutamate contribut …

Effects of MDPV on dopamine transporter regulation in male rats. Comparison with cocaine.

RATIONALE: MDPV (3,4-methylenedioxypyrovalerone) is a synthetic cathinone present in bath salts. It is a powerful psychostimulant and blocker of the dopamine transporter (DAT), like cocaine. It is known that acute exposure to psychostimulants induces rapid changes in DAT function. OBJECTIVES: To investigate the effects of MDPV on DAT function comparing with cocaine. METHODS: Binding of [3H]WIN 35428 was performed on PC 12 cells treated with MDPV and washed. Rat striatal synaptosomes were incubated with MDPV or cocaine (1 μM) for 1 h and [3H]dopamine (DA) uptake was performed. Also, different…

Genetic deletion of the dopamine D3 receptor increases vulnerability to heroin in mice.

Despite extensive research, the neurobiological risk factors that convey vulnerability to opioid abuse are still unknown. Recent studies suggest that the dopamine D3 receptor (D3R) is involved in opioid self-administration, but it remains unclear whether altered D3R availability is a risk factor for the development of opioid abuse and addiction. Here we used dopamine D3 receptor-knockout (D3-KO) mice to investigate the role of this receptor in the different phases of opioid addiction. D3-KO mice learned to self-administer heroin faster and took more heroin than wild-type mice during acquisitio…

Sensory attenuation in Parkinson's disease is related to disease severity and dopamine dose.

Abnormal initiation and control of voluntary movements are among the principal manifestations of Parkinson's disease (PD). However, the processes underlying these abnormalities and their potential remediation by dopamine treatment remain poorly understood. Normally, movements depend on the integration of sensory information with the predicted consequences of action. This integration leads to a suppression in the intensity of predicted sensations, reflected in a 'sensory attenuation'. We examined this integration process and its relation to dopamine in PD, by measuring sensory attenuation. Pati…

Impact of menopause on outcomes in prolactinomas after dopamine agonist treatment withdrawal.

OBJECTIVE: Discontinuation of dopamine agonist (DA) treatment in women with prolactinoma after menopause is a potential approach; studies systematically assessing long-term outcomes are lacking. Our aim was to investigate the natural history of prolactinoma in this group. DESIGN/PATIENTS: Retrospective cohort study of women with prolactinoma diagnosed before menopause and who after menopause were not on DA. RESULTS: Thirty women were included. Twenty-eight received DA (median duration 18 years, median age at DA withdrawal 52 years). At last assessment (median follow-up 3 years) and compared …

The dopamine hypothesis of bipolar affective disorder: the state of the art and implications for treatment.

Bipolar affective disorder is a common neuropsychiatric disorder. Although its neurobiological underpinnings are incompletely understood, the dopamine hypothesis has been a key theory of the pathophysiology of both manic and depressive phases of the illness for over four decades. The increased use of antidopaminergics in the treatment of this disorder and new in vivo neuroimaging and post-mortem studies makes it timely to review this theory. To do this, we conducted a systematic search for post-mortem, pharmacological, functional magnetic resonance and molecular imaging studies of dopamine fun…

Advances and challenges in the search for D2 and D3 dopamine receptor-selective compounds.

Compounds that target D2-like dopamine receptors (DRs) are currently used as therapeutics for several neuropsychiatric disorders including schizophrenia (antagonists) and Parkinson's disease (agonists). However, as the D2R and D3R subtypes are highly homologous, creating compounds with sufficient subtype-selectivity as well as drug-like properties for therapeutic use has proved challenging. This review summarizes the progress that has been made in developing D2R- or D3R-selective antagonists and agonists, and also describes the experimental conditions that need to be considered when determinin…

Dopamine Modulates Adaptive Prediction Error Coding in the Human Midbrain and Striatum.

Learning to optimally predict rewards requires agents to account for fluctuations in reward value. Recent work suggests that individuals can efficiently learn about variable rewards through adaptation of the learning rate, and coding of prediction errors relative to reward variability. Such adaptive coding has been linked to midbrain dopamine neurons in nonhuman primates, and evidence in support for a similar role of the dopaminergic system in humans is emerging from fMRI data. Here, we sought to investigate the effect of dopaminergic perturbations on adaptive prediction error coding in humans…

Progression of nonmotor symptoms in subgroups of patients with non-dopamine-deficient Parkinsonism.

BACKGROUND: Ten to fifteen percent of Parkinson's disease (PD) patients recruited to clinical trials have scans without evidence of dopaminergic deficit, whose presence represents a heterogeneous patient population. METHODS: A cohort of 41 patients with parkinsonism and scans without evidence of dopaminergic deficit at baseline, were subdivided into groups according to their final clinical diagnoses and nigrostriatal dopamine function assessed after 2 years of study. At follow up, 23 patients had clinically probable PD or unclassified parkinsonism with normal nigrostriatal dopamine imaging ("…