D2 Receptor mRNA Expression Research Articles

Mesolimbic dopamine D2 receptor plasticity contributes to stress resilience in rats subjected to chronic mild stress

RationaleFew studies have investigated neurobiological and biochemical differences between stress-resilient and stress-vulnerable experimental animals.ObjectivesWe investigated alterations in mesolimbic dopamine D2 receptor density and mRNA expression level in stressed rats at two time points, i.e. after 2 and 5 weeks of chronic mild stress (CMS).MethodsWe used the chronic mild stress paradigm because it is a well-established animal model of depression. Two groups of stressed rats were distinguished during CMS experiments: (1) stress reactive (70 %), which displayed a decrease in the drinking of a palatable sucrose solution during the stress regimen, and (2) stress resilient (30 %), which exhibited an unaltered drinking profile when compared with the unchallenged control group. [3H]Domperidone was used as a ligand to label dopamine D2 receptors, and a mixture of three specific oligonucleotides was used to evaluate dopamine D2 receptor mRNA changes in various regions of the rat brain.ResultsCMS strongly affected the mesolimbic dopamine circuit in stress-resilient group after 2 weeks and stress-reactive group of rats after 5 weeks which exhibited a decrease in the level of dopamine D2 receptor protein without alterations in D2 mRNA expression. Stress-resilient animals, but not stress-reactive animals, effectively adapted to the extended stress and coped with it. The increase in D2 mRNA expression returned the dopamine D2 receptor density to control levels in stress-resilient rats after 5 weeks of CMS, but not in stress-reactive animals.ConclusionsThese results clearly demonstrate that, despite earlier blunting, the activation of dopamine receptor biosynthesis in the dopamine mesoaccumbens system in stress-resilient rats is involved in active coping with stressful experiences, and it exhibits a delay in time.

Aberrant Dopamine D2-Like Receptor Function in a Rodent Model of Schizophrenia

Based on the observation that antipsychotic medications display antagonist properties at dopamine D2-like receptors, aberrant dopamine signaling has been proposed to underlie psychosis in patients with schizophrenia. Thus, it is not surprising that considerable research has been devoted to understanding the mechanisms involved in the antipsychotic action of these compounds. It is important to note that the majority of these studies have been performed in "normal" experimental animals. Given that these animals do not possess the aberrant neuronal information processing typically associated with schizophrenia, the aim of the current study was to examine the dopamine D2 receptor system in a rodent model of schizophrenia. Here, we demonstrate that methylazoxymethanol acetate (MAM)-treated rats display an enhanced effect of quinpirole on dopamine neuron activity and an aberrant locomotor response to D2-like receptor activation, suggesting changes in postsynaptic D2-like receptor function. To better understand the mechanisms underlying the enhanced response to D2-like ligands in MAM-treated rats, we examined the expression of D2, D3, and dopamine transporter mRNA in the nucleus accumbens and ventral tegmental area by quantitative reverse transcription-polymerase chain reaction. MAM-treated rats displayed a significant increase in dopamine D3 receptor mRNA expression in the nucleus accumbens with no significant changes in the expression of the D2 receptor. Taken together, these data demonstrate robust alterations in dopamine D2-like receptor function in a rodent model of schizophrenia and provide evidence that preclinical studies examining the mechanisms of antipsychotic drug action should be performed in animal models that mirror aspects of the abnormal neuronal transmission thought to underlie symptoms of schizophrenia.

Effects of Ningdong granule on DA, DRD2, and HVA in a rat model of Tourette's syndrome

ObjectiveNingdong granule is a traditional Chinese medicine preparation for the treatment of Tourette's syndrome. MethodsSixty-four rats were randomly assigned to a control group and three experimental groups, respectively. Rat models of Tourette's syndrome were established via intraperitoneal injection of apomorphine (Apo). The rats in the experimental groups were subsequently intragastrically injected with haloperidol at 10 mg/kg (haloperidol group), Ningdong granule at 370 mg/kg (NDG group), and normal saline (0.9%) at 10 mL/kg (Apo group), respectively. Rat behaviors were observed and recorded on a daily basis. After 12 w, all rats were sacrificed, and sera and striatal tissues were harvested. Homovanillic acid levels in sera, as well as dopamine and dopamine D2 receptor mRNA expression in the striatum, were measured to determine possible mechanisms of Ningdong granule on the dopamine system in a rat model of Tourette's syndrome. ResultsFollowing intervention, stereotype actions of the Tourette's syndrome rats were significantly inhibited in the haloperidol and NDG groups, respectively (P<0.01). Homovanillic levels were significantly greater in the haloperidol and NDG groups, respectively (P<0.05). In addition, dopamine levels were significantly less in the NDG group (P<0.01), and DRD2 mRNA expression was significantly reduced in the haloperidol and NDG groups, respectively (P<0.05). ConclusionResults demonstrated that Ningdong granule effectively inhibited stereotype actions and Tourette's syndrome symptoms by promoting dopamine metabolism, reducing dopamine levels in the striatum, increasing homovanillic acid content in sera, and reducing mRNA expression of DRD2 in the striatum.

Glucocorticoid receptor antagonism blocks ethanol-induced place preference learning in mice and attenuates dopamine D2 receptor adaptation in the frontal cortex

The glucocorticoid receptor (GR) plays an important role in alcohol (EtOH) self-administration behaviour by its interaction with the dopaminergic (DA) system in the brain. Here we asked whether the GR is also involved in the establishment of EtOH-induced conditioned place preference (CPP) by an interaction with the DA systems in terminal projection areas. We found that the establishment of an EtOH (2 g/kg, i.p.)-induced CPP was paralleled by a decrease in frontal cortex DA D2 receptor mRNA expression, but not in local D2 gene promoter methylation rate. No effect in other brain areas, nor on DA transporter or DA receptor regulating factor mRNA was found. The GR antagonist, RU486 (20 mg/kg, i.p.) blocked the establishment of EtOH CPP and prevented DA D2 receptor adaptations. These data may suggest a role of glucocorticoid receptor mediated D2 adaptations in the establishment of the reinforcing effects of EtOH.

The Dopamine D2 Receptor Gene in Lamprey, Its Expression in the Striatum and Cellular Effects of D2 Receptor Activation

All basal ganglia subnuclei have recently been identified in lampreys, the phylogenetically oldest group of vertebrates. Furthermore, the interconnectivity of these nuclei is similar to mammals and tyrosine hydroxylase-positive (dopaminergic) fibers have been detected within the input layer, the striatum. Striatal processing is critically dependent on the interplay with the dopamine system, and we explore here whether D2 receptors are expressed in the lamprey striatum and their potential role. We have identified a cDNA encoding the dopamine D2 receptor from the lamprey brain and the deduced protein sequence showed close phylogenetic relationship with other vertebrate D2 receptors, and an almost 100% identity within the transmembrane domains containing the amino acids essential for dopamine binding. There was a strong and distinct expression of D2 receptor mRNA in a subpopulation of striatal neurons, and in the same region tyrosine hydroxylase-immunoreactive synaptic terminals were identified at the ultrastructural level. The synaptic incidence of tyrosine hydroxylase-immunoreactive boutons was highest in a region ventrolateral to the compact layer of striatal neurons, a region where most striatal dendrites arborise. Application of a D2 receptor agonist modulates striatal neurons by causing a reduced spike discharge and a diminished post-inhibitory rebound. We conclude that the D2 receptor gene had already evolved in the earliest group of vertebrates, cyclostomes, when they diverged from the main vertebrate line of evolution (560 mya), and that it is expressed in striatum where it exerts similar cellular effects to that in other vertebrates. These results together with our previous published data (Stephenson-Jones et al. 2011, 2012) further emphasize the high degree of conservation of the basal ganglia, also with regard to the indirect loop, and its role as a basic mechanism for action selection in all vertebrates.

Molecular characterization of individual D3 dopamine receptor-expressing cells isolated from multiple brain regions of a novel mouse model

Among dopamine receptors, the expression and function of the D3 receptor subtype is not well understood. The receptor has the highest affinity for dopamine and many drugs that target dopamine receptors.In this paper, we examined, at the single cell level, the characteristics of D3 receptor-expressing cells isolated from different brain regions of male and female mice that were either 35 or 70 days old. The brain regions included nucleus accumbens, Islands of Calleja, olfactory tubercle,retrosplenial cortex, dorsal subiculum, mammillary body,amygdala and septum. The expression analysis was done in the drd3-enhanced green fluorescent protein transgenic mice that report the endogenous expression of D3 receptor mRNA. Using single cell reverse transcriptase PCR, we determined if the D3 receptor-expressing fluorescent cells in these mice were neurons or glia and if they were glutamatergic, GABAergic or catecholaminergic. Next, we determined if the fluorescent cells co-expressed the four other dopamine receptor subtypes, adenylate cyclase V(ACV) isoform, and three different isoforms of G protein coupled inward rectifier potassium (GIRK) channels. The results suggest that D3 receptor is expressed in neurons,with region-specific expression in glutamatergic and GABAergic neurons. The D3 receptor primarily coexpressed with D1 and D2 dopamine receptors with regional, sex and age-dependent differences in the coexpression pattern. The percentage of cells co-expressing D3 receptor and ACV or GIRK channels varied significantly by brain region, sex and age. The molecular characterization of D3 receptor-expressing cells in mouse brain reported here will facilitate the characterization of D(3) receptor function in physiology and pathophysiology.

Accelerated maternal responding following intra-VTA pertussis toxin treatment

Prior studies have supported a role for mesolimbic dopaminergic mechanisms in the regulation of maternal behavior. Accordingly, the ventral tegmental area (VTA) and its dopaminergic projections to the nucleus accumbens (NAc) and medial prefrontal cortex (mPFC) have been implicated in both the onset and maintenance of normal maternal behavior. To date, studies of direct manipulation of VTA neurochemistry at the onset of maternal behavior have been limited. The current study was undertaken to directly test the hypothesis that enhancement of dopaminergic transmission in the mesolimbic dopamine system can stimulate maternal activity using a pup-induced virgin model. Nulliparous female rats were stereotaxically infused with pertussis toxin (PTX 0, 0.1, or 0.3 μg/hemisphere) into the VTA to chronically stimulate the activity of dopaminergic projection neurons. After 3 days of recovery, maternal responding to donor pups was tested daily, and latency (in days) to full maternal behavior was recorded. Intra-VTA PTX treatment produced a robust dose-dependent decrease in maternal behavior latency, and a long-lasting increase in locomotor activity. These effects were associated with significantly decreased dopamine D1 receptor mRNA expression in the NAc. No effects of PTX treatment on mesolimbic dopamine utilization or mPFC receptor expression were observed. The findings indicate that chronic neural activation in the VTA accelerates the onset of maternal behavior in virgin female rats via modification of the NAc dopamine D1 receptor.

D1 dopamine receptor post‐transcriptional regulation in the CAD catecholaminergic cell line

The D1 dopamine receptor has been implicated in various addictive behaviors. We have demonstrated that this receptor is post‐transcriptionally regulated (PTR) both in vivo and in vitro. The objective of our study is to determine the molecular mechanisms that mediate D1 receptor PTR. The CAD catecholaminergic cell line expresses endogenous D1 receptor. Upon serum deprivation‐induced differentiation, there is an increase in D1 receptor mRNA expression but not protein. Here we show that the 3′ untranslated region (UTR) is necessary and sufficient for D1 receptor PTR. Deletion and competition studies suggest that the PTR is mediated by a trans‐acting factor interacting within the first 1277 bp of the D1 3'UTR. Dicer knockdown studies indicated a role for micro‐RNAs (miRs). To identity the miRs involved in D1 receptor PTR we compared the global expression profile of all known miRs in non‐differentiated and differentiated CAD cells. Funded by The FM Kirby Foundation and NIH (R03 DA026030) grants to EVK and a PhRMA Foundation Pre‐Doctoral Fellowship to KT.

Dopamine receptor modulation of risky decision-making

Several psychopathological disorders related to aberrant dopamine transmission are associated with sub-optimal risky decision-making. To observe the relationship between risk and receptor specific dopamine transmission in a rodent model, we tested the effects of drugs selective to D1-like and D2-like receptors on a risky decision-making task. Then, to determine if risk preference is related to dopamine receptor expression, in situ hybridization was used to quantify region-specific D1 and D2 receptor mRNA in rats characterized in risky decision-making. Agonists and antagonists specific to D1-like receptors had no effects on risky choice; however, the D2-like agonist bromocriptine reduced risky choice. D1 mRNA abundance in nucleus accumbens shell and insular cortex were both positive predictors of baseline risk preference, while D2 mRNA abundance in orbitofrontal cortex and medial prefrontal cortex predicted risky decision-making behavior in nonlinear fashion. Additionally, increased levels of D2 mRNA in dorsal striatum were observed in risk-averse rats in comparison to risk-taking rats. Risky decision-making can be directly affected (reduced) by acute D2-like receptor activation, but trait risky decision-making appears to be a function of distinct patterns of both D1 and D2 receptor mRNA expression in various frontostriatal regions.

Dopamine D2 receptor mRNA expression is increased in the jugular-nodose ganglia of rats with nitrogen dioxide-induced chronic bronchitis

The bronchodilatatory effect of inhaled dopamine or dopamine D2 receptor agonists in cases of bronchial constriction may involve the suppression of pathologically increased airway sensory nerve activity. The aim of this study is to investigate the regulation of the dopamine D2 receptor mRNA expression in the ganglia of rats with nitrogen dioxide-induced chronic bronchitis compared with that in ganglia of healthy control animals. Rats were exposed to nitrogen dioxide (10ppm, 20d) and dopamine D2 receptor mRNA levels in sensory ganglia (jugular-nodose, trigeminal, cervical dorsal root and thoracic dorsal root ganglia) were examined by quantitative real-time polymerase chain reaction and compared to control tissues. Whereas for trigeminal and dorsal root ganglia the dopamine D2 receptor expression levels showed no difference between both animal groups, there was a significant (p<0.05) increase in the jugular-nodose ganglia with a 2.1-fold factor. The increase of dopamine D2 receptor mRNA in jugular-nodose sensory neurons which innervate the airways may represent a neurochemical basis for the effects seen in man and animal models following topical administration of dopamine or dopamine agonists onto the respiratory epithelium.

Developmental changes in the mRNA expression of neuropeptides and dopamine and glutamate receptors in neonates and adult rats after ventral hippocampal lesion

BackgroundThe neurodevelopment of hippocampus and prefrontal cortex are known to influence different functions in normal and pathological conditions including cognition and sensorimotor functions. The neonatal lesion of the ventral hippocampus (VH) in rats has been established as an animal model of schizophrenia and is used to study postpubertal changes in behavior and neurobiology. In order to investigate whether early VH lesion in rats alters the expression of genes implicated in schizophrenia pre- and post-puberty, we studied the mRNA expression of neuropeptides (substance P, dynorphin and enkephalin), dopamine D1, dopamine D2, and NMDA (subunits NR1 and NR2A) receptors in this animal model. MethodsRat pups were lesioned at postnatal day 7 by injecting ibotenic acid into the VH bilaterally, and then sacrificed at age 35 (pre-puberty) and 65 (post-puberty) days. Another group of adult rats had the same lesion in the VH, to independently assess the effects of the lesion on the expression of genes, and then sacrificed at week 4 and 8 post lesion. Sham groups were injected with cerebrospinal fluid using the same procedure. Brains were removed and sectioned to study the mRNA expression using in situ hybridization (ISH). ResultsThe main results are the postpubertal onset of increased NR1 mRNA expression in all cortical regions and decreased dopamine D2 receptor, substance P and enkephalin mRNA expression in the striatum only in rats lesioned as neonates. These changes were not observed in the adult group with VH lesion. ConclusionsOur results demonstrate that the postpubertal behavioral changes in this animal model (and possibly schizophrenia) are related to postpubertal onset of changes in the development of functions and interactions of the dopamine and glutamate receptors in the mesocortical system.

Aripiprazole differentially affects mesolimbic and nigrostriatal dopaminergic transmission: implications for long-term drug efficacy and low extrapyramidal side-effects

Aripiprazole has been used effectively to treat schizophrenia in the clinic; however, its mechanisms of action are not clear. This study examined how short- and long-term aripiprazole treatment affects dopaminergic transmission in mesolimbic and nigrostriatal pathways. For comparison, the effects of haloperidol and olanzapine treatment were also examined. Aripiprazole significantly increased D2 receptor mRNA expression and decreased tyrosine hydroxylase (TH) mRNA expression in the ventral tegmental area (VTA) after 1- and 12-wk treatment, but had no effect in substantia nigra (SN) and nucleus accumbens (NAc). Aripiprazole also decreased dopamine transporter (DAT) binding density in NAc (for 1- and 12-wk treatment) and VTA (1-wk treatment). In contrast, haloperidol significantly increased D2 receptor binding density and decreased DAT binding density in NAc and caudate putamen (CPu) after 1- and 12-wk treatment, and it also decreases DAT binding in VTA after 12-wk treatment. Olanzapine had less widespread effects, namely an increase in D2 receptor mRNA in VTA after 12-wk treatment and decreased DAT binding in NAc after 1-wk treatment. These results suggest that aripiprazole has selective effects on the mesolimbic dopaminergic pathway. Selectively reducing dopamine synthesis in VTA is a possible therapeutic mechanism for the long-term efficacy of aripiprazole in controlling schizophrenia symptoms with reduced extrapyramidal side-effects.

Unaltered D1, D2, D4, and D5 dopamine receptor mRNA expression and distribution in the spinal cord of the D3 receptor knockout mouse

Dopamine (DA) acts through five receptor subtypes (D1-D5). We compared expression levels and distribution patterns of all DA mRNA receptors in the spinal cord of wild-type (WT) and loss of function D3 receptor knockout (D3KO) animals. D3 mRNA expression was increased in D3KO, but no D3 receptor protein was associated with cell membranes, supporting the previously reported lack of function. In contrast, mRNA expression levels and distribution patterns of D1, D2, D4, and D5 receptors were similar between WT and D3KO animals. We conclude that D3KO spinal neurons do not compensate for the loss of function of the D3 receptor with changes in the other DA receptor subtypes. This supports use of D3KO animals as a model to provide insight into D3 receptor dysfunction in the spinal cord.

Cotreatment with the kappa opioid agonist U69593 enhances locomotor sensitization to the D2/D3 dopamine agonist quinpirole and alters dopamine D2 receptor and prodynorphin mRNA expression in rats

The repeated coadministration of the kappa opioid receptor agonist U69593 with the D2/D3 dopamine (DA) agonist quinpirole (QNP) potentiates locomotor sensitization induced by QNP. Behavioral evidence has implicated both pre- and postsynaptic changes as being involved in this augmentation. The objectives of this study were to obtain supporting molecular evidence of pre- and/or postsynaptic alterations in the DA system with U69593/QNP cotreatment and to examine the relationship of such changes to locomotor sensitization. Gene expression of D1 and D2 receptors (D1R and D2R), the DA transporter, as well as the endogenous opioid prodynorphin (DYN), in the basal ganglia was examined by in situ hybridization in rats after one or ten drug injections. After one injection, changes that were specific to U69593/QNP cotreatment were decreased D1R and D2R messenger RNA (mRNA) in the nucleus accumbens (Acb) shell and increased DYN mRNA in the dorsal striatum (STR). After ten injections, U69593/QNP-specific changes were decreased D2R mRNA in substantia nigra (SN) and increased DYN mRNA in STR and Acb core. Only in U69593/QNP rats was the sensitized locomotor performance on injection ten positively correlated with DYN mRNA levels in Acb and STR. Distinct alterations of D2R and DYN mRNA levels in SN and Acb/STR, respectively, strengthen the evidence implicating pre- and postsynaptic changes in augmented locomotor sensitization to U69593/QNP cotreatment. It is suggested that repeated U69593/QNP cotreatment may augment locomotor sensitization to QNP by activating D1R-expressing DYN neurons and attenuating presynaptic D2R function.

Extracellular cAMP inhibits D1 dopamine receptor expression in CAD catecholaminergic cells via A2a adenosine receptors

The expression of D1 dopamine (DA) receptor gene is regulated during development, aging, and pathophysiology. The extracellular factors and signaling mechanisms that modulate the expression of D1 DA receptor have not been well characterized. Here, we present novel evidence that endogenous D1 DA receptor expression is inhibited by extracellular cAMP in the Cath.A Derived (CAD) catecholaminergic neuronal cell line. CAD cells express the multi-drug resistance protein 5 transporters and secrete cAMP. Addition of exogenous cAMP decreases D1 receptor mRNA and protein greater than fourfold in 24 h. The cAMP-induced decrease of D1 receptor mRNA levels is blocked by cGMP and by 1,3-dipropyl-8-(p-sulfo-phenyl)xanthine, an inhibitor of ecto-phosphodiestrase. Extracellular AMP, a metabolite of cAMP, also independently decreased D1 receptor mRNA levels. Inhibitors of ecto-nucleotidases, alpha,beta-methyleneadenosine 5'-di-phosphate and GMP, completely blocked the decrease of D1 receptor mRNA by extracellular cAMP, but only partially blocked the decrease induced by extracellular AMP. Levamisole, an inhibitor of tissue non-specific alkaline phosphatase, completely blocked the AMP-induced decrease of D1 receptor mRNA. The extracellular cAMP, AMP, and adenosine (ADO)-induced decrease in D1 receptor mRNA expression are mediated by A2a ADO receptor subtype. The results suggest a novel molecular mechanism linking activation of A2a ADO receptors with inhibition of D1 DA receptor expression.

Influence of Morphine and Dopamine Receptor Sensitization on Locomotor Activity in Mice

In the present study, the influence of morphine- and dopamine receptor antagonists-induced sensitization on morphine-induced locomotion in mice was investigated. Morphine (30, 40 and 50 mg/kg) increased, while lower doses of the opioid (10 and 20 mg/kg) decreased locomotor activity of mice. Subchronic repeated pretreatment of animals with morphine showed an increase in locomotion induced by the opioid. Clozapine reduced locomotor activity induced by morphine in both the naïve and subchronic morphine- treated animals. Subchronic pretreatment of clozapine also caused an increase in the locomotion induced by morphine. Sulpiride also decreased locomotion induced by morphine and its subchronic administration of the drug caused an increase in morphine- or apomorphine-induced locomotion. Co-administration of clozapine with sulpiride did not elicit potentiation in inhibiting the morphine effect. The D2 receptor mRNA expression was also increased by repeated morphine administration. It may be concluded that morphine-induced sensitization may be due to increase in D2 receptor mRNA expression. Sulpiride and clozapine may induce sensitization and also inhibit morphine-induced locomotion through their dopamine receptor blocking properties.

The Neuroscience of Pleasure. Focus on “Ventral Pallidum Firing Codes Hedonic Reward: When a Bad Taste Turns Good”

For more than 2,000 years, philosophers have struggled to define, let alone explain, pleasure or hedonics. With contemporary animal models and techniques, scientists now have the ability to provide a comprehensive description of this affective state by examining its neural underpinnings. In this issue of the Journal of Neurophysiology (p. 2399 –2409), Tindell and colleagues use an elegant, reductionist approach to take a profound step in defining these neural foundations (Tindell 2006). The authors control for various elements of reward that historically have confounded researchers ambitious enough to attempt to study such an intangible topic. Specifically, Tindell and colleagues establish a role for ventral pallidum (VP) neurons in encoding hedonics. The authors infused an unpalatable concentration of saline into the oral cavities of rats while recording the extracellular electrophysiological activity of single VP neurons. Aversive orofacial reactions to the unpalatable taste were simultaneously measured. Three days later, rats were made sodium deplete and retested. In a sodium-depleted state, these rats now exhibited a behavioral switch from aversive taste reactivity to appetitive taste reactivity coincident with increased VP activity to the infusion of saline (similar to responses for a palatable sucrose solution). The clever implicit controls indicate that the altered electrophysiological activity encodes a hedonic shift rather than alterations in motivated behavior or sensory coding.

Neonatal caffeine augments the acute breathing frequency response to hypoxia and the adenosine and the dopamine receptor mRNA expression in the carotid body of adult rats

Neonatal caffeine treatment (NCT), used to treat apnea of prematurity, increases persistently the hypercapnic ventilatory response of adult rats. However, the influence of NCT on the ventilatory response to hypoxia is unknown. The aim of this study was to determine the consequences of NCT on 1) the ventilatory response to hypoxia (12% of O2) of adult male and female rats and 2) the tyrosine hydroxylase, the adenosine, and the dopamine receptor mRNA expression in the carotid bodies. To this aim, plethysmographic measurements were performed on male and female adult rats previously subjected to either water (control) or caffeine 15 mg/kg (NCT) administration during the neonatal period (postnatal days 3 to 12). Tyrosine hydroxylase, adenosine, and dopamine receptor mRNA quantification in the carotid bodies was estimated by RT-PCR also. NCT enhanced the immediate frequency response on the onset of hypoxia in a sex-specific manner (male only). Results of RT-PCR analysis showed that NCT augments tyrosine hydroxylase, adenosine A2A and dopamine D2 receptor mRNA expression in the carotid bodies of males, but not of females. Thus, the sex-specific increase of the hypoxic ventilatory response induced by NCT could be due to an increase of adenosine A2A and/or dopamine D2 receptor expression observed only in the carotid bodies of males. Supported by the Foundation for the Research into Children's Disease, and the Jeanne-and-Jean-Louis-Levesque’ Chair in Perinatalogy.

D3 dopamine receptor mRNA is elevated in T cells of schizophrenic patients whereas D4 dopamine receptor mRNA is reduced in CD4 +-T cells

The expression of dopamine receptors was examined in purified human neutrophils, monocytes, B cells, natural killer cells and CD4 +- and CD8 +-T lymphocytes by RT-PCR. In healthy subjects, D1 and D2 receptors were not expressed in leukocytes. Real Time PCR for dopamine receptors D3 and D4 disclosed that D3 receptors are expressed in T cells and natural killer cells and D4 receptors in CD4 +-T cells. The comparison of schizophrenic patients with sex- and age-matched controls revealed a significantly higher expression of D3 receptor mRNA in T cells of schizophrenic patients, whereas D4 receptor mRNA in CD4 +-T cells was downregulated.

Dopamine type 2 receptor expression and function in rodent sensory neurons projecting to the airways

Agonists of the dopamine receptors have been demonstrated to have bronchodilatory properties in pathologically constricted airways. The mechanism by which these agonists induce bronchodilatation is thought to involve airway sensory nerves. In this study, the expression and function of dopamine D(2) receptor were examined in sensory ganglia supplying the airways. Neuronal dopamine D(2) receptor mRNA expression was demonstrated by single-cell RT-PCR following laser-assisted microdissection. The projection of the neurons to the airways was confirmed by retrograde neuronal labeling. In functional studies, dopamine D(2) receptor agonists (AR-C65116AB and ropinirole) inhibited intraneuronal calcium mobilization in rat capsaicin-sensitive primary sensory neurons and capsaicin-induced plasma extravasation in the rat trachea. Our results provide support to the hypothesis that dopamine D(2) receptor activation inhibits neurogenic inflammation and proinflammatory reflex responses.