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Frontiers in Bioscience (Elite Edition) Jan 2013Dopamine is a neurotransmitter that is utilized in brain circuits associated with reward processing and motor activity. Advances in microelectrode techniques and cyclic... (Review)
Review
Dopamine is a neurotransmitter that is utilized in brain circuits associated with reward processing and motor activity. Advances in microelectrode techniques and cyclic voltammetry have enabled its extracellular concentration fluctuations to be examined on a subsecond time scale in the brain of anesthetized and freely moving animals. The microelectrodes can be attached to micropipettes that allow local drug delivery at the site of measurement. Drugs that inhibit dopamine uptake or its autoreceptors can be evaluated while only affecting the brain region directly adjacent to the electrode. The drugs are ejected by iontophoresis in which an electrical current forces the movement of molecules by a combination of electrical migration and electroosmosis. Using electroactive tracer molecules, the amount ejected can be measured with cyclic voltammetry. In this review we will give an introduction to the basic principles of iontophoresis, including a historical account on the development of iontophoresis. It will also include an overview of the use of iontophoresis to study neurotransmission of dopamine in the rat brain. It will close by summarizing the advantages of iontophoresis and how the development of quantitative iontophoresis will facilitate future studies.
Topics: Animals; Corpus Striatum; Dopamine; Drug Delivery Systems; Iontophoresis; Microelectrodes; Rats; Synaptic Transmission
PubMed: 23276986
DOI: 10.2741/e612 -
Neuron Oct 2002
Review
Topics: Animals; Behavior; Decision Making; Dopamine; Humans; Reward
PubMed: 12383776
DOI: 10.1016/s0896-6273(02)00973-x -
Dialogues in Clinical Neuroscience 2006In contrast to the conventional view of dopamine involvement in schizophrenia, which posits hyperactive dopaminergic transmission, we propose that for unknown... (Review)
Review
In contrast to the conventional view of dopamine involvement in schizophrenia, which posits hyperactive dopaminergic transmission, we propose that for unknown developmental and/or biochemical reasons, a primary defect occurs in efficient, tight dopaminergic synaptic transmission, triggering feedback activation and receptor upregulation, and resulting in the well-characterized increase in dopaminergic tone. This hypothesis is driven by suggestive evidence for subpopulations of dopamine D2 receptors delivering contrasting forms of dopaminergic transmission: synaptic receptors, responsible for basic dopaminergic function and subject to effective feedback control, and poorly controlled extrasynaptic receptors partly responsible for the positive symptoms of psychosis. Since the primary defect is dopamine deficiency, we term this theory the dopaminergic deficit hypothesis of schizophrenia. It is currently informing clinical studies with novel partial dopamine antagonists (dopamine stabilizers) such as ACR16, which preferentially target extrasynaptic receptors while leaving synaptic transmission and basic dopamine function intact.
Topics: Animals; Antipsychotic Agents; Dopamine; Dopamine Agonists; Dopamine Antagonists; Humans; Models, Neurological; Receptors, Dopamine D2; Schizophrenia
PubMed: 16640125
DOI: 10.31887/DCNS.2006.8.1/acarlsson -
Experimental Eye Research Nov 2020Animal models have demonstrated a link between dysregulation of the retinal dopamine system and the development of experimental myopia (short-sightedness). However,...
PURPOSE
Animal models have demonstrated a link between dysregulation of the retinal dopamine system and the development of experimental myopia (short-sightedness). However, pharmacological investigations of dopamine in animal models rely heavily on intravitreal or systemic administration, which have several limitations for longer-term experiments. We therefore investigated whether administration of dopamine as a topical eye drop can inhibit the development of form-deprivation myopia (FDM) in chicks. We also examined whether chemical modification of dopamine through deuterium substitution, which might enhance stability and bioavailability, can increase dopamine's effectiveness against FDM when given topically.
METHODS
Dopamine or deuterated dopamine (Dopamine-1,1,2,2-d hydrochloride) was administered as a daily intravitreal injection or as daily topical eye drops to chicks developing FDM over an ascending dose range (min. n = 6 per group). Axial length and refraction were measured following 4 days of treatment.
RESULTS
Both intravitreal (ED = 0.002μmoles) and topical application (ED = 6.10μmoles) of dopamine inhibited the development of FDM in a dose-dependent manner. Intravitreal injections, however, elicited a significantly higher level of protection relative to topical eye drops (p < 0.01). Deuterated dopamine inhibited FDM to a similar extent as unmodified dopamine when administered as intravitreal injections (p = 0.897) or topical eye drops (p = 0.921).
CONCLUSIONS
Both intravitreal and topical application of dopamine inhibit the development of FDM in a dose-dependent manner, indicating that topical administration may be an effective avenue for longer-term dopamine experiments. Deuterium substitution does not alter the protection afforded by dopamine against FDM when given as either an intravitreal injection or topical eye drop.
Topics: Animals; Chickens; Disease Models, Animal; Dopamine; Dopamine Agents; Male; Myopia; Ophthalmic Solutions; Refraction, Ocular; Treatment Outcome
PubMed: 32919992
DOI: 10.1016/j.exer.2020.108233 -
Journal of Medicine and Life 2014Many drugs targeting dopaminergic system were developed for treating schizophrenia (antagonists of D2 dopaminergic receptors, e.g. antipsychotics) or Parkinson' disease... (Review)
Review
Many drugs targeting dopaminergic system were developed for treating schizophrenia (antagonists of D2 dopaminergic receptors, e.g. antipsychotics) or Parkinson' disease (agonists of dopaminergic receptors, e.g. L-DOPA). Because many of the patients treated with these drugs consume caffeine based beverages, pharmacodynamics and pharmacokinetics interactions between caffeine and dopaminergic system or drugs influencing this system are possible. The present review is assessing the current available scientific data on pharmacodynamics interactions between the dopaminergic and adenosinergic system but also on caffeine and dopaminergic system interactions. Caffeine can significantly improve Parkinson's disease symptoms but also the extrapyramidal syndrome induced by antipsychotics via dopaminergic pathways. No study so far has directly evaluated the influence of caffeine in schizophrenia, but there is growing evidence that adenosine dysfunction may contribute to the neurobiological and clinical features of schizophrenia. Caffeine has also effects on the reward system but it seems that this effect does not involve dopaminergic system. Caffeine has some endocrine effects via dopaminergic system such as decreasing the milk production in lactating women or other potential reproductive and nutritional consequences.
Topics: Animals; Brain; Caffeine; Dopamine; Humans; Neurodegenerative Diseases; Receptors, Dopamine; Receptors, Purinergic P1
PubMed: 27057246
DOI: No ID Found -
Neuron Mar 2008By distinguishing groups of dopamine neurons that differ in their projection patterns and intrinsic properties, Lammel and colleagues report in this issue of Neuron that... (Review)
Review
By distinguishing groups of dopamine neurons that differ in their projection patterns and intrinsic properties, Lammel and colleagues report in this issue of Neuron that mesocorticolimbic dopamine neurons of the ventral tegmental area (VTA) form a distinct subclass of dopamine cells.
Topics: Animals; Dopamine; Humans; Neurons; Prefrontal Cortex
PubMed: 18341984
DOI: 10.1016/j.neuron.2008.02.027 -
Journal of Ovarian Research Aug 2023Polycystic ovarian syndrome (PCOS) is a disorder with a foundation of neuroendocrine dysfunction, characterized by increased gonadotropin-releasing hormone (GnRH)...
Polycystic ovarian syndrome (PCOS) is a disorder with a foundation of neuroendocrine dysfunction, characterized by increased gonadotropin-releasing hormone (GnRH) pulsatility, which is antagonized by dopamine. The dopamine receptor 2 (DRD2), encoded by the DRD2 gene, has been shown to mediate dopamine's inhibition of GnRH neuron excitability through pre- and post-synaptic interactions in murine models. Further, DRD2 is known to mediate prolactin (PRL) inhibition by dopamine, and high blood level of PRL have been found in more than one third of women with PCOS. We recently identified PRL as a gene contributing to PCOS risk and reported DRD2 conferring risk for type 2 diabetes and depression, which can both coexist with PCOS. Given DRD2 mediating dopamine's action on neuroendocrine profiles and association with metabolic-mental states related to PCOS, polymorphisms in DRD2 may predispose to development of PCOS. Therefore, we aimed to investigate whether DRD2 variants are in linkage to and/or linkage disequilibrium (i.e., linkage and association) with PCOS in Italian families. In 212 Italian families, we tested 22 variants within the DRD2 gene for linkage and linkage disequilibrium with PCOS. We identified five novel variants significantly linked to the risk of PCOS. This is the first study to identify DRD2 as a risk gene in PCOS, however, functional studies are needed to confirm these results.
Topics: Female; Humans; Diabetes Mellitus, Type 2; Dopamine; Gonadotropin-Releasing Hormone; Polycystic Ovary Syndrome; Receptors, Dopamine D2
PubMed: 37563671
DOI: 10.1186/s13048-023-01205-2 -
Journal of Communication Disorders 2011Both limb and cranial motor functions are adversely impacted by Parkinson's disease (PD). While current pharmacological and surgical interventions are effective in... (Review)
Review
UNLABELLED
Both limb and cranial motor functions are adversely impacted by Parkinson's disease (PD). While current pharmacological and surgical interventions are effective in alleviating general limb motor symptoms of PD, they have failed to provide significant benefit for cranial motor functions. This suggests that the neuropathologies mediating limb and cranial motor impairments in PD may differ. Animal models provide a mechanism by which the potential neural dysfunctions underlying these different motor impairments may be characterized. Central goals to our laboratory have been to (a) determine the differential responses of cranial motor and limb motor function to striatal dopamine depletion and (b) determine the differential effects of striatal dopamine depletion on the integrity of cranial motor and limb motor neural circuits. This paper details the use of a comprehensive battery of limb and cranial motor behavioral tasks and the application of intracortical microstimulation to assess corticospinal and corticobulbar circuits in a rodent model of PD. Our work suggests that striatal dopamine depletion does differentially affect cranial and limb motor function and corticospinal and corticobulbar circuits. Further, we propose that cranial motor impairments in PD may be mediated by pathology both within and outside nigrostriatal dopamine system.
LEARNING OUTCOMES
Readers will be able to (a) describe a set of motor tests used to assess limb motor and cranial motor function in an animal model of Parkinson's disease, (b) understand the application of intracortical microstimulation to assess corticospinal and corticobulbar circuits, (c) describe the differential effects of dopamine depletion on limb motor and cranial motor function in a rodent model of PD, and (d) understand the potential role of dysfunction outside the nigrostriatal system mediating cranial motor impairments in Parkinson's disease.
Topics: Animals; Behavior, Animal; Corpus Striatum; Disease Models, Animal; Dopamine; Humans; Motor Skills; Movement; Neural Pathways; Neuropsychological Tests; Parkinson Disease; Rats
PubMed: 21601869
DOI: 10.1016/j.jcomdis.2011.04.008 -
Molecules (Basel, Switzerland) Dec 2017Catecholamines play an important regulatory role in cutaneous wound healing. The exact role of dopamine in human epidermis has yet to be fully elucidated. Current... (Review)
Review
Catecholamines play an important regulatory role in cutaneous wound healing. The exact role of dopamine in human epidermis has yet to be fully elucidated. Current published evidence describes its differential effects on two separate families of G protein coupled receptors: D1-like and D2-like dopamine receptors. Dopamine may enhance angiogenesis and wound healing through its action on dopamine D1 receptors, while impairing wound healing when activating D2 receptors. This review summarizes the evidence for the role of dopamine in wound healing and describes potential mechanisms behind its action on D1 versus D2-like receptors in the skin.
Topics: Animals; Cell Line; Dopamine; Humans; Receptors, Dopamine D1; Receptors, Dopamine D2; Signal Transduction; Skin; Wound Healing
PubMed: 29278360
DOI: 10.3390/molecules23010050 -
ENeuro Feb 2024Sensory cues are critical for shaping decisions and invigorating actions during reward seeking. Dopamine neurons in the ventral tegmental area (VTA) are central in this...
Sensory cues are critical for shaping decisions and invigorating actions during reward seeking. Dopamine neurons in the ventral tegmental area (VTA) are central in this process, supporting associative learning in Pavlovian and instrumental settings. Studies of intracranial self-stimulation (ICSS) behavior, which show that animals will work hard to receive stimulation of dopamine neurons, support the notion that dopamine transmits a reward or value signal to support learning. Recent studies have begun to question this, however, emphasizing dopamine's value-free functions, leaving its contribution to behavioral reinforcement somewhat muddled. Here, we investigated the role of sensory stimuli in dopamine-mediated reinforcement, using an optogenetic ICSS paradigm in tyrosine hydroxylase (TH)-Cre rats. We find that while VTA dopamine neuron activation in the absence of explicit external cues is sufficient to maintain robust self-stimulation, the presence of cues dramatically potentiates ICSS behavior. Our results support a framework where dopamine can have some base value as a reinforcer, but the impact of this signal is modulated heavily by the sensory learning context.
Topics: Rats; Animals; Dopamine; Ventral Tegmental Area; Cues; Reinforcement, Psychology; Reward; Dopaminergic Neurons
PubMed: 38238080
DOI: 10.1523/ENEURO.0421-23.2024