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Brain Research Bulletin Apr 2023Stress contributes to pain sensation by affecting several neural pathways, including mesolimbic-cortical dopamine neurons. Nucleus accumbens, an essential element of the...
Stress contributes to pain sensation by affecting several neural pathways, including mesolimbic-cortical dopamine neurons. Nucleus accumbens, an essential element of the mesolimbic dopaminergic pathway, plays a fundamental role in modulating pain and is differentially influenced by stressful events. Since we previously demonstrated the marked association of intra-NAc dopamine receptors with forced swim stress-evoked analgesia in acute pain state, this research was conducted to consider the contribution of intra-accumbal D1- and D2-like dopamine receptors to modulating effects of exposure to restraint stress in pain-related behaviors during the tail-flick test. Stereotaxic surgery was executed to implant a guide cannula within the NAc in male Wistar rats. On the test day, different concentrations of SCH23390 and Sulpiride as D1- and D2-like dopamine receptor antagonists, respectively, were unilaterally microinjected within the NAc. The vehicle animals received saline or 12 % DMSO (0.5 µl) instead of SCH23390 or Sulpiride into the NAc, respectively. Five minutes following receiving drug or vehicle, animals were restrained for 3 h and then their acute nociceptive threshold was measured for a 60-min period by the tail-flick test. Our data revealed that RS considerably enhanced antinociceptive reaction in acute pain states. The analgesia evoked by RS dramatically declined following blocking either D1- or D2-like dopamine receptors in the NAc, an effect was more noticeable by D1-like dopamine receptor antagonist. These findings indicated that intra-NAc dopamine receptors are considerably mediated in the RS-produced analgesia in acute pain states, suggesting their possible role in psychological stress and disease.
Topics: Rats; Animals; Male; Sulpiride; Rats, Wistar; Acute Pain; Receptors, Dopamine D2; Receptors, Dopamine D1; Dopamine Antagonists; Nucleus Accumbens; Analgesics
PubMed: 36889361
DOI: 10.1016/j.brainresbull.2023.03.003 -
Distinct Roles of Dopamine Receptor Subtypes in the Nucleus Accumbens during Itch Signal Processing.The Journal of Neuroscience : the... Nov 2022Ventral tegmental area (VTA) dopaminergic neurons, which are well known for their central roles in reward and motivation-related behaviors, have been shown to...
Ventral tegmental area (VTA) dopaminergic neurons, which are well known for their central roles in reward and motivation-related behaviors, have been shown to participate in itch processing via their projection to the nucleus accumbens (NAc). However, the functional roles of different dopamine receptor subtypes in subregions of the NAc during itch processing remain unknown. With pharmacological approaches, we found that the blockade of dopamine D1 receptors (D1R), but not dopamine D2 receptors (D2R), in the lateral shell (LaSh) of the NAc impaired pruritogen-induced scratching behavior in male mice. In contrast, pharmacological activation of D2R in both the LaSh and medial shell (MeSh) of the NAc attenuated the scratching behavior induced by pruritogens. Consistently, we found that dopamine release, as detected by a dopamine sensor, was elevated in the LaSh rather than the MeSh of the NAc at the onset of scratching behavior. Furthermore, the elevation of dopamine release in the LaSh of the NAc persisted even though itch-relieving behavior was blocked, suggesting that the dopamine signal in the NAc LaSh represents a motivational component of itch processing. Our study revealed different dynamics of dopamine release that target neurons expressing two dopamine receptors subtypes within different subregions of the NAc, and emphasized that D1R in the LaSh of the NAc is important in itch signal processing. Dopamine has been implicated in itch signal processing. However, the mechanism underlying the functional role of dopamine in itch processing remains largely unknown. Here, we examined the role of dopamine D1 receptor (D1R) and D2R in the nucleus accumbens (NAc) shell during pruritogen-induced scratching behavior. We demonstrated that D1R in the NAc lateral shell (LaSh) play an important role in motivating itch-induced scratching behavior, while activation of D2R would terminate scratching behavior. Our study revealed the diverse functional roles of dopamine signals in the NAc shell during itch processing.
Topics: Male; Mice; Animals; Nucleus Accumbens; Receptors, Dopamine D1; Ventral Tegmental Area; Receptors, Dopamine D2; Dopamine; Dopaminergic Neurons; Pruritus
PubMed: 36241382
DOI: 10.1523/JNEUROSCI.0821-22.2022 -
PloS One 2017The propensity to exhibit social behaviors during interactions with same-sex and opposite-sex conspecifics is modulated by various neurotransmitters, including dopamine....
The propensity to exhibit social behaviors during interactions with same-sex and opposite-sex conspecifics is modulated by various neurotransmitters, including dopamine. Dopamine is a conserved neurotransmitter among vertebrates and dopaminergic receptors are also highly conserved among taxa. Activation of D1 and D2 dopamine receptor subtypes has been shown to modulate social behaviors, especially in mammalian and avian studies. However, the specific behavioral functions of these receptors vary across taxa. In reptiles there have been few studies examining the relationship between dopaminergic receptors and social behaviors. We therefore examined the effects of D1 and D2 agonists and antagonists on sexual and aggressive behaviors in the male green anole lizard (Anolis carolinensis). Treatment with high doses of both D1 and D2 agonists was found to impair both sexual and aggressive behaviors. However, the D1 agonist treatment was also found to impair motor function, suggesting that those effects were likely nonspecific. Lower doses of both agonists and antagonists failed to affect social behaviors. These findings provide some evidence for D2 receptor regulation of social behaviors, but in contrast with previous research, these effects are all inhibitory and no effects were found for manipulations of D1 receptors. A potential reason for the lack of more widespread effects on social behaviors using moderate or low drug doses is that systemic injection of drugs resulted in effects throughout the whole brain, thus affecting counteracting circuits which negated one another, making measurable changes in behavioral output difficult to detect. Future studies should administer drugs directly into brain regions known to regulate sexual and aggressive behaviors.
Topics: Aggression; Animals; Dopamine D2 Receptor Antagonists; Female; Lizards; Male; Motor Activity; Receptors, Dopamine D1; Receptors, Dopamine D2; Sexual Behavior, Animal; Social Behavior
PubMed: 28187160
DOI: 10.1371/journal.pone.0172041 -
The Journal of Neuroscience : the... Jul 2003By stimulating distinct receptor subtypes, dopamine (DA) exerts presynaptic and postsynaptic actions on both large aspiny (LA) cholinergic and fast-spiking (FS)...
By stimulating distinct receptor subtypes, dopamine (DA) exerts presynaptic and postsynaptic actions on both large aspiny (LA) cholinergic and fast-spiking (FS) parvalbumin-positive interneurons of the striatum. Lack of receptor- and isoform-specific pharmacological agents, however, has hampered the progress toward a detailed identification of the specific DA receptors involved in these actions. To overcome this issue, in the present study we used four different mutant mice in which the expression of specific DA receptors was ablated. In D1 receptor null mice, D1R-/-, DA dose-dependently depolarized both LA and FS interneurons. Interestingly, SCH 233390 (10 microm), a D1-like (D1 and D5) receptor antagonist, but not l-sulpiride (3-10 microm), a D2-like (D2, D3, D4) receptor blocker, prevented this effect, implying D5 receptors in this action. Accordingly, immunohistochemical analyses in both wild-type and D1R-/- mice confirmed the expression of D5 receptors in both cholinergic and parvalbumin-positive interneurons of the striatum. In mice lacking D2 receptors, D2R-/-, the DA-dependent inhibition of GABA transmission was lost in both interneuron populations. Both isoforms of D2 receptor, D2L and D2S, were very likely involved in this inhibitory action, as revealed by the electrophysiological analysis of the effect of the DA D2-like receptor agonist quinpirole in two distinct mutants lacking D2L receptors and expressing variable contents of D2S receptors. The identification of the receptor subtypes involved in the actions of DA on different populations of striatal cells is essential to understand the circuitry of the basal ganglia and to develop pharmacological strategies able to interfere selectively with specific neuronal functions.
Topics: Animals; Antibody Specificity; Blotting, Western; Corpus Striatum; Dopamine; Dopamine Agonists; Electrophysiology; In Vitro Techniques; Interneurons; Male; Membrane Potentials; Mice; Mice, Knockout; Patch-Clamp Techniques; Presynaptic Terminals; Protein Isoforms; Receptors, Dopamine; Receptors, Dopamine D1; Receptors, Dopamine D2; Receptors, Dopamine D5; Receptors, GABA-A; Synapses
PubMed: 12867509
DOI: 10.1523/JNEUROSCI.23-15-06245.2003 -
Journal of Pharmacological Sciences 2012Randomized clinical trials have shown that pramipexole has an antidepressant effect in patients with Parkinson's disease. We investigated the comparative efficacy of...
Randomized clinical trials have shown that pramipexole has an antidepressant effect in patients with Parkinson's disease. We investigated the comparative efficacy of pramipexole toward dopamine receptor D(2) and D(3) expression in rat brain. Groups of rats were treated subacutely with pramipexole (1 mg/kg), imipramine (10 mg/kg), or bromocriptine (5 mg/kg), with appropriate controls. Using real-time RT-PCR and immunoblotting, dopamine receptor D(2) and D(3) expression was up-regulated in the striatum following pramipexole treatment, while imipramine and bromocriptine had no significant effects. These findings support that pramipexole exerts additional therapeutic benefits such as decreasing depression by increasing dopamine receptor D(3) expression in the striatum.
Topics: Animals; Benzothiazoles; Blotting, Western; Corpus Striatum; Dopamine Agonists; Male; Pramipexole; RNA, Messenger; Rats; Rats, Wistar; Real-Time Polymerase Chain Reaction; Receptors, Dopamine D2; Receptors, Dopamine D3; Up-Regulation
PubMed: 22986363
DOI: 10.1254/jphs.12096sc -
Polish Journal of Pharmacology 2004Dopamine mediates its biological actions via at least five distinct G protein-coupled receptors. Recently, significant progress has been made in the understanding of the... (Review)
Review
Dopamine mediates its biological actions via at least five distinct G protein-coupled receptors. Recently, significant progress has been made in the understanding of the molecular and cellular consequences of activation of the different dopamine receptors. Not only their anatomical localization has been revisited, what implicates new insights into well known D1/D2 receptor synergism, but also evidence has been provided that dopamine receptors can physically interact with each other as well as with other neurotransmitter receptors. Dopamine receptors are subject to phosphorylation by G protein-coupled receptor kinases, the specificity of which has started to be revealed. Some progress has been made in elucidating the functional significance of polymorphisms observed in genes encoding dopamine receptor. All these new findings need to be appreciated by the psychopharmacologists in order to better understand the behavioral consequences of activation of dopamine receptors.
Topics: Animals; Brain; Receptors, Dopamine
PubMed: 15662079
DOI: No ID Found -
Pharmacology & Therapeutics Nov 1998During the past decade, it has become evident that dopamine plays an important role in the regulation of renal function and blood pressure. Dopamine exerts its actions... (Review)
Review
During the past decade, it has become evident that dopamine plays an important role in the regulation of renal function and blood pressure. Dopamine exerts its actions via a class of cell-surface receptors coupled to G-proteins that belong to the rhodopsin family. Dopamine receptors have been classified into two families based on pharmacologic and molecular cloning studies. In mammals, two D1-like receptors that have been cloned, the D1 and D5 receptors (known as D1A and D1B, respectively, in rodents), are linked to stimulation of adenylyl cyclase. Three D2-like receptors that have been cloned (D2, D3, and D4) are linked to inhibition of adenylyl cyclase and Ca2+ channels and stimulation of K+ channels. All the mammalian dopamine receptors, initially cloned from the brain, have been found to be expressed outside the central nervous system, in such sites as the adrenal gland, blood vessels, carotid body, intestines, heart, parathyroid gland, and the kidney and urinary tract. Dopamine receptor subtypes are differentially expressed along the nephron, where they regulate renal hemodynamics and electrolyte and water transport, as well as renin secretion. The ability of renal proximal tubules to produce dopamine and the presence of receptors in these tubules suggest that dopamine can act in an autocrine or paracrine fashion; this action becomes most evident during extracellular fluid volume expansion. This renal autocrine/paracrine function is lost in essential hypertension and in some animal models of genetic hypertension; disruption of the D1 or D3 receptor produces hypertension in mice. In humans with essential hypertension, renal dopamine production in response to sodium loading is often impaired and may contribute to the hypertension. The molecular basis for the dopaminergic dysfunction in hypertension is not known, but may involve an abnormal post-translational modification of the dopamine receptor.
Topics: Animals; Dopamine; Glomerular Filtration Rate; Humans; Hypertension; Kidney; Kidney Diseases; Receptors, Dopamine; Renal Circulation; Sodium
PubMed: 9839770
DOI: 10.1016/s0163-7258(98)00027-8 -
Brain and Behavior Nov 2019Pyrovalerone (4-methyl-β-keto-prolintane) is a synthetic cathinone (beta-keto-amphetamine) derivative. Cathinones are a concern as drugs of abuse, as related street...
INTRODUCTION
Pyrovalerone (4-methyl-β-keto-prolintane) is a synthetic cathinone (beta-keto-amphetamine) derivative. Cathinones are a concern as drugs of abuse, as related street drugs such as methylenedioxypyrovalerone have garnered significant attention. The primary mechanism of action of cathinones is to inhibit reuptake transporters (dopamine and norepinephrine) in reward centers of the central nervous system.
METHODS
We measured bioenergetic, behavioral, and molecular responses to pyrovalerone (nM-µM) in zebrafish to evaluate its potential for neurotoxicity and neurological impairment.
RESULTS
Pyrovalerone did not induce any mortality in zebrafish larvae over a 3- and 24-hr period; however, seizures were prevalent at the highest dose tested (100 µM). Oxidative phosphorylation was not affected in the embryos, and there was no change in superoxide dismutase 1 expression. Following a 3-hr treatment to pyrovalerone (1-100 µM), larval zebrafish (6d) showed a dose-dependent decrease (70%-90%) in total distance moved in a visual motor response (VMR) test. We interrogated potential mechanisms related to the hypoactivity, focusing on the expression of dopamine-related transcripts as cathinones can modulate the dopamine system. Pyrovalerone decreased the expression levels of dopamine receptor D1 (~60%) in larval zebrafish but did not affect the expression of tyrosine hydroxylase, dopamine active transporter, or any other dopamine receptor subunit examined, suggesting that pyrovalerone may regulate the expression of dopamine receptors in a specific manner.
DISCUSSION
Further studies using zebrafish are expected to reveal new insight into molecular mechanisms and behavioral responses to cathinone derivates, and zebrafish may be a useful model for understanding the relationship between the dopamine system and bath salts.
Topics: Animals; Central Nervous System Stimulants; Dopamine; Dopamine Plasma Membrane Transport Proteins; Larva; Locomotion; Oxidative Phosphorylation; Pyrrolidines; Receptors, Dopamine; Receptors, Dopamine D1; Seizures; Superoxide Dismutase-1; Tyrosine 3-Monooxygenase; Zebrafish
PubMed: 31625691
DOI: 10.1002/brb3.1420 -
American Journal of Physiology. Heart... Feb 2008Dopamine plays an important role in the pathogenesis of hypertension by regulating epithelial sodium transport and by interacting with vasoactive hormones/humoral... (Review)
Review
Dopamine plays an important role in the pathogenesis of hypertension by regulating epithelial sodium transport and by interacting with vasoactive hormones/humoral factors, such as aldosterone, angiotensin, catecholamines, endothelin, oxytocin, prolactin pro-opiomelancortin, reactive oxygen species, renin, and vasopressin. Dopamine receptors are classified into D(1)-like (D(1) and D(5)) and D(2)-like (D(2), D(3), and D(4)) subtypes based on their structure and pharmacology. In recent years, mice deficient in one or more of the five dopamine receptor subtypes have been generated, leading to a better understanding of the physiological role of each of the dopamine receptor subtypes. This review summarizes the results from studies of various dopamine receptor mutant mice on the role of individual dopamine receptor subtypes and their interactions with other G protein-coupled receptors in the regulation of blood pressure.
Topics: Animals; Blood Pressure; Dopamine; Hypertension; Mice; Mice, Knockout; Receptors, Dopamine; Receptors, Dopamine D1; Receptors, Dopamine D2; Receptors, Dopamine D3; Receptors, Dopamine D4; Receptors, Dopamine D5
PubMed: 18083900
DOI: 10.1152/ajpheart.01036.2007 -
Journal of Neurochemistry Aug 2003The neurotransmitter dopamine plays an important role in the regulation of behavior in both vertebrates and invertebrates. In mammals, dopamine binds and activates two...
The neurotransmitter dopamine plays an important role in the regulation of behavior in both vertebrates and invertebrates. In mammals, dopamine binds and activates two classes of dopamine receptors, D1-like and D2-like receptors. However, D2-like dopamine receptors in Caenorhabditis elegans have not yet been characterized. We have cloned a cDNA encoding a putative C. elegans D2-like dopamine receptor. The deduced amino acid sequence of the cloned cDNA shows higher sequence similarities to vertebrate D2-like dopamine receptors than to D1-like receptors. Two splice variants that differ in the length of their predicted third intracellular loops were identified. The receptor heterologously expressed in cultured cells showed high affinity binding to [125I]iodo-lysergic acid diethylamide. Dopamine showed the highest affinity for this receptor among several amine neurotransmitters tested. Activation of the heterologously expressed receptor led to the inhibition of cyclic AMP production, confirming that this receptor has the functional property of a D2-like receptor. We have also analyzed the expression pattern of this receptor and found that the receptor is expressed in several neurons including all the dopaminergic neurons in C. elegans.
Topics: Alternative Splicing; Amino Acid Sequence; Animals; CHO Cells; COS Cells; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Cloning, Molecular; Colforsin; Cricetinae; Cyclic AMP; Female; Male; Molecular Sequence Data; Ovary; Phylogeny; Receptors, Dopamine D2
PubMed: 12887685
DOI: 10.1046/j.1471-4159.2003.01896.x