Dopamine Receptor Gene Expression Research Articles

Circulatory levels of dopamine and glutamate and assessment of gene expression of dopamine and glutamate receptors in patients with schizophrenia. A case control study

Circulatory levels of dopamine and glutamate and assessment of gene expression of dopamine and glutamate receptors in patients with schizophrenia. A case control study

Enhanced methamphetamine sensitisation in a rat model of the brain-derived neurotrophic factor Val66Met variant: Sex differences and dopamine receptor gene expression

Brain-derived neurotrophic factor (BDNF) and the Val66Met polymorphism may play a role in the development of psychosis and schizophrenia. The aim of this study was to investigate long-term effects of methamphetamine (Meth) on psychosis-like behaviour and dopamine receptor and dopamine transporter gene expression in a novel rat model of the BDNF Val66Met polymorphism. At the end of a 7-day subchronic Meth treatment, female rats with the Met/Met genotype selectively showed locomotor hyperactivity sensitisation to the acute effect of Meth. Male rats showed tolerance to Meth irrespective of Val66Met genotype. Two weeks later, female Met/Met rats showed increased locomotor activity following both saline treatment or a low dose of Meth, a hyperactivity which was not observed in other genotypes or in males. Baseline PPI did not differ between the groups but the disruption of PPI by acute treatment with apomorphine was absent in Meth-pretreated Met/Met rats. Female Met/Met rats selectively showed down-regulation of dopamine D2 receptor gene expression in striatum. Behavioural effects of MK-801 or its locomotor sensitisation by prior Meth pretreatment were not influenced by genotype. These data suggest a selective vulnerability of female Met/Met rats to short-term and long-term effects of Meth, which could model increased vulnerability to psychosis development associated with the BDNF Val66Met polymorphism.

Locomotor Behavior and Memory Dysfunction Induced by 3-Nitropropionic Acid in Adult Zebrafish: Modulation of Dopaminergic Signaling.

Huntington's disease (HD) is a progressive neurodegenerative disease characterized by neuropsychiatric disturbance, cognitive impairment, and locomotor dysfunction. In the early stage (chorea) of HD, expression of dopamine D2 receptors (D2R) is reduced, whereas dopamine (DA) levels are increased. Contrary, in the late stage (bradykinesia), DA levels and the expression of D2R and dopamine D1 receptors (D1R) are reduced. 3-Nitropropionic acid (3-NPA) is a toxin that may replicate HD behavioral phenotypes and biochemical aspects. This study assessed the neurotransmitter levels, dopamine receptor gene expression, and the effect of acute exposure to quinpirole (D2R agonist) and eticlopride (D2R antagonist) in an HD model induced by 3-NPA in adult zebrafish. Quinpirole and eticlopride were acutely applied by i.p. injection in adult zebrafish after chronic treatment of 3-NPA (60mg/kg). 3-NPA treatment caused a reduction in DA, glutamate, and serotonin levels. Quinpirole reversed the bradykinesia and memory loss induced by 3-NPA. Together, these data showed that 3-NPA acts on the dopaminergic system and causes biochemical alterations similar to late-stage HD. These data reinforce the hypothesis that DA levels are linked with locomotor and memory deficits. Thus, these findings may suggest that the use of DA agonists could be a pharmacological strategy to improve the bradykinesia and memory deficits in the late-stage HD.

Interaction of Brain-Derived Neurotrophic Factor with the Effects of Chronic Methamphetamine on Prepulse Inhibition in Mice Is Independent of Dopamine D3 Receptors.

The aim of the present study was to gain a better understanding of the role of brain-derived neurotrophic factor (BDNF) and dopamine D3 receptors in the effects of chronic methamphetamine (METH) on prepulse inhibition (PPI), an endophenotype of psychosis. We compared the effect of a three-week adolescent METH treatment protocol on the regulation of PPI in wildtype mice, BDNF heterozygous mice (HET), D3 receptor knockout mice (D3KO), and double-mutant mice (DM) with both BDNF heterozygosity and D3 receptor knockout. Chronic METH induced disruption of PPI regulation in male mice with BDNF haploinsufficiency (HET and DM), independent of D3 receptor knockout. Specifically, these mice showed reduced baseline PPI, as well as attenuated disruption of PPI induced by acute treatment with the dopamine receptor agonist, apomorphine (APO), or the glutamate NMDA receptor antagonist, MK-801. In contrast, there were no effects of BDNF heterozygosity or D3 knockout on PPI regulation in female mice. Chronic METH pretreatment induced the expected locomotor hyperactivity sensitisation, where female HET and DM mice also showed endogenous sensitisation. Differential sex-specific effects of genotype and METH pretreatment were observed on dopamine receptor and dopamine transporter gene expression in the striatum and frontal cortex. Taken together, these results show a significant involvement of BDNF in the long-term effects of METH on PPI, particularly in male mice, but these effects appear independent of D3 receptors. The role of this receptor in psychosis endophenotypes therefore remains unclear.

Effect of risperidone on morphine-induced conditioned place preference and dopamine receptor D2 gene expression in male rat hippocampus.

Previous studies suggest the possible effect of risperidone on brain reward system and D1 and D2 dopamine receptors' involvement in morphine-induced conditioned place preference (CPP). The present study was designed to investigate the effect of risperidone as an atypical antipsychotic drug on morphine-induced CPP and D2-like dopamine receptor gene expression in rat. An unbiased CPP paradigm was used to study the effect of risperidone. Intraperitoneal (i.p.) injection of risperidone (1, 2, and 4mg/kg) was performed 30min before the morphine (10mg/kg, i.p.) injection and just after the rat was placed in the CPP box. The open field test was used to assay the locomotor activity of animal. The gene expression of D2 dopamine receptor in hippocampus was measured by real-time PCR technique. The hippocampi of rats were also used for histology evaluation. Morphine-produced (10mg/kg) CPP and morphine-induced CPP were reversed only by the administration of a low dose of risperidone (1mg/kg). Low dose of risperidone (1mg/kg) showed no effect on locomotor activity but a higher dose of risperidone (2 and 4mg/kg) decreased locomotor activity. Real-time PCR data analysis revealed that the gene expression of D2 dopamine receptor had significant difference between morphine and a 1mg/kg dose of risperidone. Moreover, in histological evaluation, apoptosis was observed in the morphine group, whereas there was no evidence of apoptosis in the risperidone-treated groups. Our results suggest that risperidone (1mg/kg) reverses the morphine-induced CPP and may reduce the rewarding properties of morphine. It is also demonstrated that risperidone decreases the expression of D2 receptor in rat hippocampus. Therefore, risperidone can be considered potential adjunct therapy in morphine dependence.

Anti-proliferative effects of cabergoline nano conjugated form on lung cancer cells

Lung cancer is one of the deadliest and most drug-resistant cancers in the world. In this type of cancer, the effect of neurological factors and disruption of neurotransmitter pathways is significant. Cabergoline (CAB) is a specific dopamine receptor (DR) agonist that suppresses tumor cell proliferation and induces cell death. Since the high doses of this drug cause metabolic effects in patients, drug delivery methods have helped bring about better effects of the drug at lower doses. This study aimed to compare the effect of CAB and its nanofluid sample on the expression of DR genes on a lung cancer cell line (A549). Multi-wall carbon nanotubes conjugated with CAB were prepared using a reflux system and evaluated qualitatively. Nanofluid-containing nanodrug was delivered to lung cancer cells (A549) and normal cells (MRC-5) and evaluated by an MTT assay and flow cytometry. Then, the expression of DR genes was studied by real-time polymerase chain reaction before and after the treatment by drug and nanodrug. The findings revealed that nanodrug has a significant lethal influence on cancer cells. In addition, the findings showed the death of cancer cells located in the lung at a lower dose than the pure drug; however, it was not toxic to MRC-5 cells. The design of this nano-targeted drug delivery system showed that it could be a new strategy for the treatment of non-small-cell lung cancer, increase drug delivery efficiency, and consequently induce apoptosis in cancer cells while reducing drug-induced side effects in normal cells.

Dopamine Receptors Gene Expression Pattern and Locomotor Improvement Differ Between Female and Male Zebrafish During Spinal Cord Auto Repair.

The dopaminergic system, a spinal cord (SC) motor circuit regulator, is administrated by sexual hormones and evolutionary conserved in all vertebrates. Accordingly, we hypothesized that the dopamine receptor (DAR) expression pattern may be dissimilar in female and male zebrafish SC auto repair. We implemented an uncomplicated method to induce spinal cord injury (SCI) on fully reproductive adult zebrafish, in both genders. SCI was induced using a 28-gauge needle at 9th-10th vertebra without skin incision. Thereupon, lesioned SC was harvested for DAR gene expression analysis; zebrafish were tracked routinely for any improvement in swim distance, speed, and their roaming capabilities/preference. Our findings revealed discrepancies between drd2a, drd2b, drd3, drd4a, and drd4b expression patterns at 1, 7, and 14 days postinjury (DPI) between female and male zebrafish. The receptors were mostly upregulated at 7 DPI in both genders, whereas drd2a and drd2b were mostly maximized in females. Surprisingly, drd3 was measured greater even in intact SC in males. In addition, female zebrafish were able to swim farther distances more accelerated, in multiple directions, by engaging more caudal muscles compared with males, of course with no statistical significance. Indeed, females were able to generate whole-body rotation and move forward using the muscles downstream to the lesion site, whereas the coordinated movement in males was accomplished by rostral muscles. In conclusion, there are differences in DAR gene expression pattern throughout SC autonomous recovery between adult female and male zebrafish, and also, female locomotion seems to ameliorate more rapidly.

Effect of chronic stress on the relative level of dopamine receptor gene expression

Background. The regulation of the central dopaminergic system under the influence of chronic stress is disturbed, however, the dynamics of changes in the dopamine receptors expression in the periphery remains poorly understood.
 Aim. Evaluation of the different models of chronic stress influence on changes in the relative level of dopamine receptor gene expression in peripheral blood cells of rats during immobilization and intense physical activity.
 Material and methods. For 270 days on 88 Wistar rats, the study on the effect of different models of chronic stress on the change in the relative level of Drd15 genes expression was performed in four groups: the first control group; the second group was subjected to intensive physical activity in the Forced swimming with a load test (7-minute swimming with a load of 8% of body weight 2 times a week); the third group experienced daily 90-minute immobilization for 14 days; the fourth group had combined exposure of physical activity and immobilization. The relative level of dopamine receptor gene expression was determined by real-time polymerase chain reaction after 90, 180, and 270 days of the experiment in peripheral blood cells of the tail vein. The calculation of the relative level of gene expression was carried out based on the Livak method (2Ct); the assessment of the difference significance using a two-sample t-test for independent samples.
 Results. The analysis of the relative level of genes encoding D1-type dopamine receptors expression showed that a decrease in the Drd1 gene expression level after 90 days of the experiment was detected only in male rats from immobilization stress and control groups [RQ 0.35 (p=0.003) and 0.21 (p=0.002), respectively], while in males from other groups and females, the activity of this gene did not change significantly throughout the course of the experiment. The relative expression level of Drd5 gene changed only in female rats. In females subjected to intense physical activity, the level of this gene expression increased almost 4 times (RQ 3.82, p=0.005) 90 days after the start of the experiment, and in females of the control group, the transcriptional activity of the gene decreased 4 times after 180 days of the experiment (RQ 0.25, p=0.015). When assessing changes in the activity of genes encoding D2-type receptors for the Drd3 and Drd4 genes, a significant increase in the relative expression level was revealed in all experimental groups, both in males and females, on the 180th day of exposure to stress factors. At the same time, activation of both genes was occurred after 90 days in the control group only in females and persisted up to another 90 days, after which it returned to the initial level. Expression of the Drd2 gene wasn't detected in rat blood cells.
 Conclusion. The relative level of expression of D1- and D2-like receptor genes in rat peripheral blood cells depends on the type of chronic stress and has pronounced sexual dimorphism.

Differential effects of chronic adolescent glucocorticoid or methamphetamine on drug-induced locomotor hyperactivity and disruption of prepulse inhibition in adulthood in mice

Sensitization of dopaminergic activity has been suggested as an underlying mechanism in the psychotic symptoms of schizophrenia. Adolescent stress and chronic abuse of methamphetamine (Meth) are well-known risk factors for psychosis and schizophrenia; however it remains unknown how these factors compare in terms of dopaminergic behavioural sensitization in adulthood. In addition, while Brain-Derived Neurotrophic Factor (BDNF) has been implicated in dopaminergic activity and schizophrenia, its role in behavioural sensitization remains unclear. In this study we therefore compared the effect of chronic adolescent treatment with the stress hormone, corticosterone (Cort), or with Meth, on drug-induced locomotor hyperactivity and disruption of prepulse inhibition in adulthood in BDNF heterozygous mice and their wild-type controls, as well as on dopamine receptor gene expression. Between 6 and 9 weeks of age, the animals either received Cort in the drinking water or were treated with an escalating Meth dose protocol. In adulthood, Cort-pretreated mice showed significantly reduced Meth-induced locomotor hyperactivity compared to vehicle-pretreated mice. In contrast, Meth hyperlocomotion was significantly enhanced in animals pretreated with the drug in adolescence. There were no effects of either pretreatment on prepulse inhibition. BDNF Het mice showed greater Meth-induced hyperlocomotion and lower prepulse inhibition than WT mice. There were no effects of either pretreatment on D1 or D2 gene expression in either the dorsal or ventral striatum, while D3 mRNA was shown to be reduced in male mice only irrespective of genotype. These results suggest that in adolescence, chronically elevated glucocorticoid levels, a component of chronic stress, do not cause dopaminergic sensitization adulthood, in contrast to the effect of chronic Meth treatment in the same age period. BDNF does not appear to be involved in the effects of chronic Cort or chronic Meth.

Differential Expression of Three Dopamine Receptors in Varroa-Resistant Honey Bees.

Various stocks of honey bees (Apis mellifera L. (Hymenoptera: Apidae)) employ multiple mechanisms to control varroa mite (Varroa destructor Anderson & Trueman (Mesostigmata: Varroidae)) infestations. Identification of trait-associated genes and markers can improve efficiency of selective breeding. Dopamine receptors show promise in this regard in their association with numerous traits in honey bees, high plasticity, and indicated association with varroa resistance through QTL analysis. We assessed the relationship between exposure to mite-infested brood and gene expression of the honey bee dopamine receptors, Amdop1, Amdop2, and Amdop3, in bees and stocks with known levels of varroa resistance, in Spring 2016 (VSH vs Italian) and Summer 2019 (Pol-line vs Italian). Relative mRNA expression levels varied both by honey bee stock and before/after exposure to varroa-infested brood, in 7-, 10-, and 14-day-old bees. However, the trials revealed contrasting patterns in expression of the three dopamine receptors. In 2016, downregulation was evident in VSH bees, but varied by days post-emergence and by gene. The 2019 trial showed upregulation post-exposure in both stocks, and at all ages, for Amdop1, Amdop2, and Amdop3, with the exception of 14 d Italian bees for Amdop2 and Amdop3. Stock comparison in 2019 showed upregulation of all three dopamine-like receptors in post-exposure bees of all ages. Season and associated differences in mite loads may have contributed to the differences observed across trials. Differential expression of all three dopamine receptors suggests a role for the dopaminergic system in varroa resistance and suggests that further characterization of these receptors for breeding potential is warranted.

A mind in motion: Exercise improves cognitive flexibility, impulsivity and alters dopamine receptor gene expression in a Parkinsonian rat model

Cognitive impairment, particularly deficits in executive function (EF) is common in Parkinson's disease (PD) and may lead to dementia. There are currently no effective treatments for cognitive impairment. Work from our lab and others has shown that physical exercise may improve motor performance in PD but its role in cognitive function remains poorly eludicated. In this study in a rodent model of PD, we sought to examine whether exercise improves cognitive processing and flexibility, important features of EF. Rats received 6-hydroxydopamine lesions of the bilateral striatum (caudate-putamen, CPu), specifically the dorsomedial CPu, a brain region central to EF. Rats were exercised on motorized running wheels or horizontal treadmills for 6-12 weeks. EF-related behaviors including attention and processing, as well as flexibility (inhibition) were evaluated using either an operant 3-choice serial reaction time task (3-CSRT) with rule reversal (3-CSRT-R), or a T-maze task with reversal. Changes in striatal transcript expression of dopamine receptors (Drd1-4) and synaptic proteins (Synaptophysin, PSD-95) were separately examined following 4 weeks of exercise in a subset of rats. Exercise/Lesion rats showed a modest, yet significant improvement in processing-related response accuracy in the 3-CSRT-R and T-maze, as well as a significant improvement in cognitive flexibility as assessed by inhibitory aptitude in the 3-CSRT-R. By four weeks, exercise also elicited increased expression of Drd1, Drd3, Drd4, synaptophysin, and PSD-95 in the dorsomedial and dorsolateral CPu. Our results underscore the observation that exercise, in addition to improving motor function may benefit cognitive performance, specifically EF, and that early changes (by 4 weeks) in CPu dopamine modulation and synaptic connectivity may underlie these benefits.

Dopamine Levels Induced by Substance Abuse Alter Efficacy of Maraviroc and Expression of CCR5 Conformations on Myeloid Cells: Implications for NeuroHIV.

Despite widespread use of antiretroviral therapy (ART), HIV remains a major public health issue. Even with effective ART many infected individuals still suffer from the constellation of neurological symptoms now known as neuroHIV. These symptoms can be exacerbated by substance abuse, a common comorbidity among HIV-infected individuals. The mechanism(s) by which different types of drugs impact neuroHIV remains unclear, but all drugs of abuse increase central nervous system (CNS) dopamine and elevated dopamine increases HIV infection and inflammation in human myeloid cells including macrophages and microglia, the primary targets for HIV in the brain. Thus, drug-induced increases in CNS dopamine may be a common mechanism by which distinct addictive substances alter neuroHIV. Myeloid cells are generally infected by HIV strains that use the chemokine receptor CCR5 as a co-receptor, and our data indicate that in a subset of individuals, drug-induced levels of dopamine could interfere with the effectiveness of the CCR5 inhibitor Maraviroc. CCR5 can adopt distinct conformations that differentially regulate the efficiency of HIV entry and subsequent replication and using qPCR, flow cytometry, Western blotting and high content fluorescent imaging, we show that dopamine alters the expression of specific CCR5 conformations of CCR5 on the surface of human macrophages. These changes are not affected by association with lipid rafts, but do correlate with dopamine receptor gene expression levels, specifically higher levels of D1-like dopamine receptors. These data also demonstrate that dopamine increases HIV replication and alters CCR5 conformations in human microglia similarly to macrophages. These data support the importance of dopamine in the development of neuroHIV and indicate that dopamine signaling pathways should be examined as a target in antiretroviral therapies specifically tailored to HIV-infected drug abusers. Further, these studies show the potential immunomodulatory role of dopamine, suggesting changes in this neurotransmitter may also affect the progression of other diseases.

Forager age and foraging state, but not cumulative foraging activity, affect biogenic amine receptor gene expression in the honeybee mushroom bodies.

Foraging behavior is crucial for the development of a honeybee colony. Biogenic amines are key mediators of learning and the transition from in-hive tasks to foraging. Foragers vary considerably in their behavior, but whether and how this behavioral diversity depends on biogenic amines is not yet well understood. For example, forager age, cumulative foraging activity or foraging state may all be linked to biogenic amine signaling. Furthermore, expression levels may fluctuate depending on daytime. We tested if these intrinsic and extrinsic factors are linked to biogenic amine signaling by quantifying the expression of octopamine, dopamine and tyramine receptor genes in the mushroom bodies, important tissues for learning and memory. We found that older foragers had a significantly higher expression of Amdop1, Amdop2, AmoctαR1, and AmoctβR1 compared to younger foragers, whereas Amtar1 showed the opposite pattern. Surprisingly, our measures of cumulative foraging activity were not related to the expression of the same receptor genes in the mushroom bodies. Furthermore, we trained foragers to collect sucrose solution at a specific time of day and tested if the foraging state of time-trained foragers affected receptor gene expression. Bees engaged in foraging had a higher expression of Amdop1 and AmoctβR3/4 than inactive foragers. Finally, the expression of Amdop1, Amdop3, AmoctαR1, and Amtar1 also varied with daytime. Our results show that receptor gene expression in forager mushroom bodies is complex and depends on both intrinsic and extrinsic factors.

Quantitative Analysis of Somatostatin and Dopamine Receptors Gene Expression Levels in Non-functioning Pituitary Tumors and Association with Clinical and Molecular Aggressiveness Features.

The primary treatment for non-functioning pituitary tumors (NFPTs) is surgery, but it is often unsuccessful. Previous studies have reported that NFPTs express receptors for somatostatin (SST1-5) and dopamine (DRDs) providing a rationale for the use of dopamine agonists and somatostatin analogues. Here, we systematically assessed SST1-5 and DRDs expression by real-time quantitative PCR (RT-qPCR) in a large group of patients with NFPTs (n = 113) and analyzed their potential association with clinical and molecular aggressiveness features. SST1-5 expression was also evaluated by immunohistochemistry. SST3 was the predominant SST subtype detected, followed by SST2, SST5, and SST1. DRD2 was the dominant DRD subtype, followed by DRD4, DRD5, and DRD1. A substantial proportion of NFPTs displayed marked expression of SST2 and SST5. No major association between SSTs and DRDs expression and clinical and molecular aggressiveness features was observed in NFPTs.

Propranolol decreases DRD3 and SLC1A2 gene expression in patients with essential tremor

BackgroundEssential tremor (ET) is the most common disease among movement disorders. Genes such as essential tremor 1-4 (ETM 1-4), HS1-binding protein-3 (HS1BP3), dopamine receptor D3 (DRD3), leucine-rich repeat and Ig domain containing 1 (LINGO1), glial high affinity glutamate transporter member 2 (SLC1A2), FUS, high temperature requirement A2 (HTRA2) and TENM4 had been shown to be responsible for the genetic inheritance of the disease. The aim of the present study was to investigate the effect of propranolol on the expression of DRD3, SLC1A2, and HTRA2 genes in patients with ET.MethodsA study of non-randomized experimental design was conducted involving 76 subjects. They were divided into two groups: 38 patients with ET in the patient group (Group 1) and 38 healthy people in the control group (Group 2). DRD3, SLC1A2 and HTRA2 gene expressions were assessed before and after 8 weeks of propranolol treatment. Fahn-Tolosa-Marin tremor scale results were compared before and after propranolol administration. Kruskal Wallis test was used to determine differences in gene expressions between the groups.ResultsD3 dopamine receptor and SLC1A2 gene expression in the patient group appeared to be lower than in the control group (p<0.001). However, the HTRA2 gene expression level was significantly higher in the patient group (p<0.001). Conclusion D3 dopamine receptor and SLC1A2 gene expressions were decreased in ET patients which at first glance can be explained in relation to etiology, but after treatment it was not increased as expected but decreased even more.

The Role of the Gut‐Brain Axis in the Capacity for Learning in Zebrafish

Starved (low calorie) and overfed (high calorie) diets are common in food insecure areas and can shift gut microbiota diversity. While there is increasing evidence linking the gut microbiota composition to psychiatric disorders including anxiety and depression, little is known regarding the impact gut microbes have on learning behavior and capacity. Current literature supports that alterations in intestinal microbiota diversity and richness can influence serotonergic and dopaminergic neurotransmission. The aim of this study is to examine the influence of gut‐brain axis on learning capacity. We hypothesize that a decrease in microbial diversity and abundance will negatively impact learning in zebrafish. Fish were grouped and fed a control diet, a starved low caloric diet and an overfed high caloric diet. Afterwards microbial DNA and RNA from zebrafish brain tissue was isolated. Bacterial abundance was quantified with primers designed against 16s ribosomal RNA. Dopamine and serotonin receptor expression was examined using TaqMan primer probes. Overfed fish exhibited a significant increase weight relative to starved fish, in addition starved fish displayed a 7.0 mg decrease in weight (p<.001, n=5). Both overfed and starved fish exhibited a decrease in intestinal microbial abundance. Associative learning was assessed using a plus‐maze protocol. Interestingly we observed modest, though not significant increases in learning in the starved fish relative to overfed and control fish. Coinciding with this data, overfed fish showed no significant changes in serotonin or dopamine receptor gene expression compared to control diets, however starved diets illustrated an increasing trend in serotonin receptor expression and a significant increase in dopamine D1 receptor expression (p<.04, n=11). These results indicate that starved and overfed diets decrease gut microbial abundance and may influence learning capacity through the gut‐brain axis in starved fish.Support or Funding InformationElon University

Dopamine concentrations and dopamine receptor gene expression in emotion-related brain structures of female adult rats exposed to stress of chronic isolation from weaning.

It is known that early-life stress events induce profound consequences on emotional brain regions including amygdala, involved in emotional processing and the ventral tegmental area (VTA), which contains neuron cell bodies of the mesolimbic dopaminergic system. The aim of this study is to test the hypothesis that stress induced by long-term social isolation from weaning in female rats is associated with alterations in amygdalar dopamine receptor gene expression and VTA dopamine concentrations. Rats were weaned on postnatal day 21 and then exposed to stress of chronic isolation for 9 weeks. Control animals were housed socially. Amygdalar dopamine D1 but not D2 receptor gene expression was decreased in isolated rats compared to controls. Dopamine concentrations in the VTA were enhanced following chronic isolation. A negative correlation was observed between amygdalar D1 gene expression and dopamine concentrations in the VTA. In conclusion, a reduction of dopamine D1 receptor gene expression in the amygdala in response to stress induced by chronic isolation in female rats was accompanied by an increase in dopamine concentration in the VTA. Further studies are needed to understand the physiological significance, if any, of negative association of amygdalar dopamine receptor D1 gene expression and dopamine concentrations in the VTA.

Mechanisms behind interactive effects of temperature and bifenthrin on the predator avoidance behaviors in parr of chinook salmon (Oncorhynchus tshawytscha)

Many coastal systems have been experiencing the effects of non-chemical and chemical anthropological stressors through respective increases in surface water temperatures and rainstorm-derived runoff events of pyrethroid pesticide movement into waterways such as the San Francisco Bay-Delta. Salmonid populations in the Bay-Delta have been dramatically declining in recent decades. Therefore, the aim of this study was to investigate the interactive effects of bifenthrin, a pyrethroid insecticide, and increasing water temperatures on targeted neuroendocrine and behavioral responses in Chinook salmon (Oncorhynchus tshawytscha) parr (10- month post-hatch). Parr were reared at 11 °C, 16.4 °C, or 19 °C for 14 days and, in the final 96 h of rearing, exposed to nominal concentrations of 0, 0.15, or 1.5 μg/L bifenthrin. A predatory avoidance Y-Maze behavioral assay was conducted immediately following exposures. Parr were presented a choice of clean or odorant zones, and locomotive behavior was recorded. Thyroid hormones (T3 and T4), estradiol, and testosterone were quantified within plasma using ELISAs, and the expression of brain hormone and dopamine receptor genes were also evaluated by qPCR. Brain dopamine levels were analyzed by LC/MS. No significant changes were observed in brain transcripts or plasma hormone concentrations with bifenthrin or increasing temperature. However, temperature did significantly lower brain dopamine levels in fish reared at 19 °C compared to 11 °C controls, but was unaltered by bifenthrin treatment. In contrast, parr reared at 11 °C and exposed to 1.5 μg/L bifenthrin spent significantly less time avoiding a predatory odorant compared to vehicle controls reared at 11 °C. The 16.4 °C and 1.5 μg/L-treated fish spent significantly more time in the neutral arm compared to the odorant and clean arms, as well as spending significantly less time in the clean arm compared to the 11 °C control fish. These results suggest that the interaction of temperature and bifenthrin may be adversely impacting predator-avoidance behavior, which may not be related to dopaminergic responses.

Impact of COMT haplotypes on functional connectivity density and its association with the gene expression of dopamine receptors.

Catechol-O-methyltransferase (COMT) affects brain connectivity via modulating the dopamine system, with an expected greater effect of haplotypes than single-nucleotide polymorphism (SNP). The action pathway from COMT to dopamine to connectivity is theoretically dependent on the gene expression of dopamine receptors. Here, we aimed to investigate the impact of COMT haplotypes on brain functional connectivity density (FCD) in hundreds of healthy young subjects, and to disclose the association between the COMT-FCD statistical map and the spatial expression of the dopamine receptor genes. We found an inverted U-shaped modulation of COMT haplotypes on FCD in the left inferior parietal lobule that is mainly connected to the frontal and parietal cortices, with APS homozygotes exhibiting greater FCD than the other five groups. However, we failed to identify any significant effect of any SNP on FCD. Utilizing gene expression data collected from Allen human brain atlas, we found the COMT-FCD statistical map was significantly associated with the expression patterns of the dopamine receptor genes. Our results suggest that COMT haplotypes have greater impact on functional connectivity than a single genetic variation and that the association between COMT and functional connectivity may be dependent on the gene expression of dopamine receptors.

The Expression of Dopamine Receptors Gene and their Potential Role in Targeting Breast Cancer Cells with Selective Agonist and Antagonist Drugs. Could it be the Novel Insight to Therapy?

Breast cancer is one of the common causes of mortality for women in Iran and other parts of the world. The substantial increasing rate of breast cancer in both developed and developing countries warns the scientists to provide more preventive steps and therapeutic measures. This study is conducted to investigate the impact of neurotransmitters (e.g., Dopamine) through their receptors and the importance of cancers via damaging immune system. It also evaluates dopamine receptors gene expression in the women with breast cancer at stages II or III and dopamine receptor D2 (DRD2) related agonist and antagonist drug effects on human breast cancer cells, including MCF-7 and SKBR-3. The patients were categorized into two groups: 30 native patients who were diagnosed with breast cancer at stages II and III, with the mean age of 44.6 years and they were reported to have the experience of a chronic stress or unpleasant life event. The second group included 30 individuals with the mean age of 39 years as the control group. In order to determine the RNA concentration in all samples, the RNA samples were extracted and cDNA was synthesized. The MCF-7 cells and SKBR-3 cells were treated with dopamine receptors agonists and antagonists. The MTT test was conducted to identify oxidative and reductive enzymes and to specify appropriate dosage at four concentrations of dopamine and Cabergoline on MCF-7 and SKBR-3 cells. Immunofluorescence staining was done by the use of a mixed dye containing acridine orange and ethidiume bromide on account of differentiating between apoptotic and necrotic cells. Flow cytometry assay was an applied method to differentiate necrotic from apoptotic cells. Sixty seven and thirty three percent of the patients were related to stages II and III, respectively. About sixty three percent of the patients expressed ER, while fifty seven percent expressed PR. Thirty seven percent of the patients were identified as HER-2 positive. All types of D2-receptors were expressed in PBMC of patients with breast cancer and healthy individuals. The expression of the whole dopamine receptor subtypes (DRD2-DRD4) was carried out on MCF-7 cell line. The results of RT-PCR confirmed the expression of DRD2 on SKBR-3 cells, whereas the other types of D2- receptors did not have an expression. The remarkable differences in gene expression rates between patients and healthy individuals were revealed in the result of the Real-time PCR analysis. The over expression in DRD2 and DRD4 genes of PBMCs was observed in the patients with breast cancer at stages II and III. The great amount of apoptosis and necrosis occurred after the treatment of MCF-7 cells by Cabergoline from 25 to 100 µmolL-1 concentrations. This study revealed the features of dopamine receptors associated with apoptosis induction in breast cancer cells. Moreover, the use of D2-agonist based on dopamine receptors expression in various breast tumoral cells could be promising as a new insight of complementary therapy in breast cancer.