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#33662528   2021/03/01 To Up

Maternal Morphine Exposure and Post-Weaning Social Isolation Impair Memory and Ventral Striatum Dopamine System in Male Offspring: Is an Enriched Environment Beneficial?

Maternal opioids abuse has some deleterious consequences on next generations. Besides, children's rearing conditions can affect the behavioral states and brain plasticity in their later life. In the present study, we investigated the effects of maternal morphine (MOR) treatment and post-weaning rearing conditions on memory, pain threshold, and the ventral striatum dopaminergic activity in male offspring. Female Wistar rats were treated twice daily either with escalating doses of MOR or with normal saline (NS) one week before mating, during pregnancy and lactation. After weaning, the male pups were assigned to six groups and then raised for an 8-week period under three different conditions: standard (STD), isolated (ISO) or enriched environment (EE). The behavioral tests, including passive avoidance task, novel object recognition, and tail-flick test, were also performed. Moreover, the ventral striatum dopamine's content (DA), mRNA expressions of dopamine receptor 1(D1R) and dopamine receptor 2 (D2R), and dopamine transporter (DAT) were evaluated. The obtained data showed that maternal MOR exposure and post-weaning social isolation could dramatically impair memory in offspring, while EE could reverse these adverse outcomes. Moreover, results of tail flick latency indicated the increased pain threshold in EE animals. At molecular level, maternal MOR injections and social isolation reduced DA levels and altered expressions of D1R, D2R, and DAT within the ventral striatum of these male offspring. However, post-weaning EE partially buffered these changes. Our finding signified the effects of maternal MOR exposure and social isolation on the behaviors and neurochemistry of brain in next generation, and it also provided evidence on reversibility of these alterations following EE.
Neda Yazdanfar, Seyed Ali Mard, Javad Mahmoudi, Nima Bakhtiari, Alireza Sarkaki, Alireza Farnam

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#33650480   2021/03/02 To Up

Late effects of early weaning on food preference and the dopaminergic and endocannabinoid systems in male and female rats.

Early weaning (EW) is associated with obesity later in life. Here, using an EW model in rats, we investigated changes in feeding behavior and the dopaminergic and endocannabinoid systems (ECS) in the adult offspring. Lactating Wistar rats were divided into two groups: EW, dams were wrapped with a bandage to interrupt suckling during the last 3 days of breastfeeding; CONT; dams fed the pups throughout the period without hindrances. EW animals were compared with CONT animals of the same sex. At PN175, male and female offspring of both groups could freely self-select between high-fat and high-sugar diets (food challenge test). EW males preferred the high-fat diet at 30 min and more of the high-sugar diet after 12 h compared to CONT males. EW females did not show differences in their preference for the palatable diets compared to CONT females. Total intake of standard diet from PN30-PN180 was higher in both male and female EW animals, indicating hyperphagia. At PN180, EW males showed lower type 2 dopamine receptor (D2r) in the nucleus accumbens (NAc) and dorsal striatum, while EW females had lower tyrosine hydroxylase in the ventral tegmental area and NAc, D1r in the NAc, and D2r in the prefrontal cortex. In the lateral hypothalamus, EW males had lower fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase, whereas EW females showed lower N-arachidonoyl-phosphatidylethanolamine phospholipase-D and increased FAAH. Early weaning altered both the dopaminergic and ECS parameters at adulthood, contributing to the eating behavior changes of the progeny in a sex-dependent manner.
Patricia Novaes Soares, Rosiane Aparecida Miranda, Iala Milene Bertasso, Carla Bruna Pietrobon, Vanessa Silva Tavares Rodrigues, Elaine de Oliveira, Alex Christian Manhães, Egberto Gaspar de Moura, Patricia Cristina Lisboa

1475 related Products with: Late effects of early weaning on food preference and the dopaminergic and endocannabinoid systems in male and female rats.

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#33457337   2020/10/30 To Up

Microinjection of a Dopamine-D1 Receptor Agonist into the Ventral Tegmental Area Reverses the Blocked Expression of Morphine Conditioned Place Preference by N-Methyl-D-Aspartate Receptor Antagonist.

The release of dopamine (DA) in the posterior ventral tegmental area (pVTA) plays an important role in cue-related learning, reward, and relapse. On the other hand, studies have shown that the use of N-methyl-D-aspartate receptor (NMDAR) antagonist (AP5) inhibits the expression of morphine (5 mg/kg, s. c) conditioned place preference (CPP). In this study, we have tried to show the interaction effect of the DA stimulatory agents through D1-like receptor (D1R) agonist (SKF38393) and D2-like receptor (D2R) antagonist (eticlopride; through disinhibition) with NMDAR antagonist into the pVTA on the expression of morphine CPP.
Seyed Mostafa Ahmadian, Parisa Ghahremani, Hojjatallah Alaei

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#33349836   // To Up

[Chronic stress increases dopamine levels in hippocampal dentate gyrus and impairs spatial learning and memory in rats].

The objective of this study was to elucidate the effect of chronic stress (CS) on dopamine (DA) level and synaptic efficiency in the hippocampal dentate gyrus (DG) during spatial learning and memory. Sprague Dawley (SD) male rats were randomly divided into control group and CS group (n = 10). CS group was treated with chronic mild unpredictable stress, and control group did not receive any treatments. The levels of epinephrine and corticosterone (CORT) in serum were measured by using enzyme-linked immunosorbent assay (ELISA); the spatial learning and memory abilities of rats were measured by Morris water maze (MWM) test. Meanwhile, the amplitude of field excitatory postsynaptic potential (fEPSP) and concentration of DA in the DG region were determined by in vivo electrophysiology, microdialysis and HPLC techniques during MWM test in rats. After that, the DA D1 receptor (D1R) and its key downstream members in DG were examined by immunohistochemistry or Western blot assay. The results showed that the levels of epinephrine and CORT in the serum of the rats in CS group were significantly increased compared with those in the control group (P < 0.05). In CS group rats, the escape latency was significantly prolonged and the number of platform crossing was markedly decreased during MWM test, compared with those in control group (P < 0.05). Furthermore, the amplitude of fEPSP in the DG was not changed during MWM test in CS rats, while it was significantly increased on the 3rd day of MWM test in control group (P < 0.05). Compared with baseline or control group, CS group showed significantly increased DA level from the 1st to 3rd days of MWM test in the DG (P < 0.05). In addition, the protein expression of D1R was markedly up-regulated in the DG in CS group, while the protein expression levels of p-PKA, p-CREB and BDNF were significantly reduced, compared with those in control group. These results suggest that CS may impair spatial learning and memory abilities in rats through the enhancement of the DA levels in the hippocampal DG.
Ke Zhao, Peng Ren, Ming-Yue Li, Qing-Hua Jin, Bin Xiao

2231 related Products with: [Chronic stress increases dopamine levels in hippocampal dentate gyrus and impairs spatial learning and memory in rats].

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#33241478   2020/11/25 To Up

Shifts in the neurobiological mechanisms motivating cocaine use with the development of an addiction-like phenotype in male rats.

The development of addiction is accompanied by a shift in the mechanisms motivating cocaine use from nucleus accumbens (NAc) dopamine D receptor (DR) signaling to glutamate AMPA-kainate receptor (AMPA-R) signaling.
Wendy J Lynch, Anousheh Bakhti-Suroosh, Jean M Abel, Camilla Davis

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#33170427   2020/11/10 To Up

Orexin-A up-regulates dopamine D2 receptor and mRNA in the nucleus accumbens Shell.

Orexins-A (OrxA) and -B (OrxB) neuropeptides are synthesized by a group of neurons located in the lateral hypothalamus and adjacent perifornical area, which send their projections to the mesolimbic dopaminergic (DAergic) system including ventral tegmental area and nucleus accumbens (NAc), where orexin receptors are expressed. NAc plays a central role in reward-seeking behavior and drug abuse. NAc-neurons express dopamine-1 (D1R) and dopamine-2 (D2R) receptors. Orexins bind to their two cognate G-protein-coupled receptors, orexin-receptor type-1 (OrxR) and type-2 (OrxR). Orexin receptor signaling is involved in behaviors such as motivation and addiction. Orexin-containing neurons modulate DAergic activity that is key in synaptic plasticity induced by addictive drugs. However, the effect of OrxA on expression and content of DAergic receptors in NAc is unknown. The purpose of this study was to investigate whether OrxA can alter gene expression and protein levels of D1R/D2R in NAc. Gene expression was evaluated by real-time PCR analysis and protein levels by western blot in rats. The results show that intracerebroventricular (i.c.v.) injection of OrxA increases both gene transcription and protein content of D2R but fails to modify D1R. This effect was also confirmed with OrxA infusion in NAc/Shell. Our results demonstrate for the first time that OrxA induces up-regulation of gene and protein of D2R in NAc. These findings support the hypothesis that OrxA modulates the DAergic transmission and this may serve to understand how orexin signaling enhances DA responses at baseline conditions and in response to psychostimulants.
Sandra Morales-Mulia, Víctor Manuel Magdaleno-Madrigal, Humberto Nicolini, Alma Genis-Mendoza, Marcela Morales-Mulia

2136 related Products with: Orexin-A up-regulates dopamine D2 receptor and mRNA in the nucleus accumbens Shell.

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#33125479   2020/10/30 To Up

Functional Interplay of Type-2 Corticotrophin Releasing Factor and Dopamine Receptors in The Basolateral Amygdala-Medial Prefrontal Cortex Circuitry.

Basolateral amygdala (BLA) excitatory projections to medial prefrontal cortex (PFC) play a key role controlling stress behavior, pain and fear. Indeed, stressful events block synaptic plasticity at the BLA-PFC circuit. The stress responses involve the action of corticotrophin releasing factor (CRF) through type 1 and type 2 CRF receptors (CRF1 and CRF2). Interestingly, it has been described that dopamine receptor 1 (D1R) and CRF peptide have a modulatory role of BLA-PFC transmission. However, the participation of CRF1 and CRF2 receptors in BLA-PFC synaptic transmission still is unclear.
H E Yarur, J Zegers, I Vega-Quiroga, J Novoa, F Ciruela, M E Andres, K Gysling

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#32899459   2020/09/05 To Up

SCH23390 Reduces Methamphetamine Self-Administration and Prevents Methamphetamine-Induced Striatal LTD.

Extended-access methamphetamine self-administration results in unregulated intake of the drug; however, the role of dorsal striatal dopamine D-like receptors (DRs) in the reinforcing properties of methamphetamine under extended-access conditions is unclear. Acute (ex vivo) and chronic (in vivo) methamphetamine exposure induces neuroplastic changes in the dorsal striatum, a critical region implicated in instrumental learning. For example, methamphetamine exposure alters high-frequency stimulation (HFS)-induced long-term depression in the dorsal striatum; however, the effect of methamphetamine on HFS-induced long-term potentiation (LTP) in the dorsal striatum is unknown. In the current study, dorsal striatal infusion of SCH23390, a DR antagonist, prior to extended-access methamphetamine self-administration reduced methamphetamine addiction-like behavior. Reduced behavior was associated with reduced expression of PSD-95 in the dorsal striatum. Electrophysiological findings demonstrate that superfusion of methamphetamine reduced basal synaptic transmission and HFS-induced LTP in dorsal striatal slices, and SCH23390 prevented this effect. These results suggest that alterations in synaptic transmission and synaptic plasticity induced by acute methamphetamine via DRs could assist with methamphetamine-induced modification of corticostriatal circuits underlying the learning of goal-directed instrumental actions and formation of habits, mediating escalation of methamphetamine self-administration and methamphetamine addiction-like behavior.
Yosef Avchalumov, Wulfran Trenet, Juan Piña-Crespo, Chitra Mandyam

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#32879346   2020/09/02 To Up

Dopamine D1 receptor signalling in dyskinetic Parkinsonian rats revealed by fiber photometry using FRET-based biosensors.

As with many G protein-coupled receptors (GPCRs), the signalling pathways regulated by the dopamine D1 receptor (D1R) are dynamic, cell type-specific, and can change in the face of disease or drug exposures. In striatal neurons, the D1R activates cAMP/protein kinase A (PKA) signalling. However, in Parkinson's disease (PD), alterations in this pathway lead to functional upregulation of extracellular regulated kinases 1/2 (ERK1/2), contributing to L-DOPA-induced dyskinesia (LID). In order to detect D1R activation in vivo and to study the progressive dysregulation of D1R signalling in PD and LID, we developed ratiometric fiber-photometry with Förster resonance energy transfer (FRET) biosensors and optically detected PKA and ERK1/2 signalling in freely moving rats. We show that in Parkinsonian animals, D1R signalling through PKA and ERK1/2 is sensitized, but that following chronic treatment with L-DOPA, these pathways become partially desensitized while concurrently D1R activation leads to greater induction of dyskinesia.
Jace Jones-Tabah, Hanan Mohammad, Shadi Hadj-Youssef, Lucy E H Kim, Ryan D Martin, Faïza Benaliouad, Jason C Tanny, Paul B S Clarke, Terence E Hébert

2291 related Products with: Dopamine D1 receptor signalling in dyskinetic Parkinsonian rats revealed by fiber photometry using FRET-based biosensors.

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