scholarly journals MK-801-induced behavioral and dopaminergic responses in the shell part of the nucleus accumbens in adult rats are disrupted after neonatal blockade of the ventral subiculum

2021 ◽  
Author(s):  
Hana Saoud ◽  
Elora Kereselidze ◽  
Séverine Eybrard ◽  
Alain Louilot
Keyword(s):  
Locomotor Activity ◽  
Nucleus Accumbens ◽  
Nmda Receptors ◽  
Adult Rats ◽  
Mk 801 ◽  
Animal Modeling ◽  
Ventral Subiculum ◽  
Related Proteins ◽  
The Impact

AbstractThe present study was conducted in the context of animal modeling of schizophrenia. It investigated in adult rats, after transient neonatal blockade of the ventral subiculum (VSub), the impact of a very specific non-competitive antagonist of NMDA receptors (MK-801) on locomotor activity and dopaminergic (DAergic) responses in the dorsomedial shell part of the nucleus accumbens (Nacc), a striatal subregion described as the common target region for antipsychotics.The functional neonatal inactivation of the VSub was achieved by local microinjection of tetrodotoxin (TTX) at postnatal day 8 (PND8). Control pups were microinjected with the solvent phosphate buffered saline (PBS). Locomotor responses and DAergic variations in the dorsomedial shell part of the Nacc were measured simultaneously using in vivo voltammetry in awake, freely moving animals after sc administration of MK-801. The following results were obtained: 1) a dose-dependent increase in locomotor activity in PBS and TTX animals, greater in TTX rats/PBS rats; and 2) divergent DAergic responses for PBS and TTX animals. A decrease in DA levels with a return to around basal values was observed in PBS animals. An increase in DA levels was obtained in TTX animals. The present data suggest that neonatal blockade of the VSub results in disruption in NMDA glutamatergic transmission, causing a disturbance in DA release in the dorsomedial shell in adults rats. In the context of animal modeling of schizophrenia using the same approach it would be interesting to investigate possible changes in postsynaptic NMDA receptors-related proteins in the dorsomedial shell region in the Nacc.

scholarly journals Postnatal functional inactivation of the ventral subiculum enhances dopaminergic responses in the core part of the nucleus accumbens following ketamine injection in adult rats

2019 ◽  
Author(s):  
Hana Saoud ◽  
Duco De Beus ◽  
Séverine Eybrard ◽  
Alain Louilot
Keyword(s):  
Nucleus Accumbens ◽  
Brain Regions ◽  
Nmda Receptor Antagonist ◽  
Adult Rats ◽  
Target Region ◽  
Ventral Subiculum ◽  
New Information ◽  
Functional Inactivation ◽  
Core Part

AbstractFor almost two decades schizophrenia has been considered to be a functional disconnection disorder. This functional disconnectivity between several brain regions could have a neurodevelopmental origin. Various approaches suggest the ventral subiculum (SUB) is a particular target region for neurodevelopemental disturbances in schizophrenia. It is also commonly acknowledged that there is a striatal dopaminergic (DA) dysregulation in schizophrenia which may depend on a subiculo-striatal disconnection involving glutamatergic NMDA receptors.The present study was designed to investigate, in adult rats, the effects of the non-competitive NMDA receptor antagonist ketamine on DA responses in the ventral striatum, or, more specifically, the core part of the nucleus accumbens (Nacc), following postnatal functional inactivation of the SUB. Functional inactivation of the left SUB was carried out by local tetrodotoxin (TTX) microinjection at postnatal day 8 (PND8), i.e. at a critical point in the neurodevelopmental period. DA variations were recorded using in vivo voltammetry in freely moving adult rats (11 weeks). Locomotor activity was recorded simultaneously with the extracellular levels of DA in the core part of the Nacc. Data obtained during the present study showed that after administration of ketamine, the two indexes were higher in TTX animals than PBS animals, the suggestion being that animals microinjected with TTX in the left SUB at PND8 present greater reactivity to ketamine than animals microinjected with PBS. These findings could provide new information regarding the involvement of NMDA glutamatergic receptors in the core part of the Nacc in the pathophysiology of schizophrenia.

scholarly journals Exposure to cyclic intermittent hypoxia increases expression of functional NMDA receptors in the rat carotid body

2009 ◽  
Vol 106 (1) ◽  
pp. 259-267 ◽  
Author(s):  
Yuzhen Liu ◽  
En-Sheng Ji ◽  
Shuanglin Xiang ◽  
Renaud Tamisier ◽  
Jingli Tong ◽  
...  
Keyword(s):  
Nmda Receptors ◽  
Carotid Body ◽  
Intermittent Hypoxia ◽  
Acute Hypoxia ◽  
Sprague Dawley ◽  
Excitatory Neurotransmitter ◽  
Mk 801 ◽  
Baseline Activity ◽  
Nmda Receptor Blocker

Although large quantities of glutamate are found in the carotid body, to date this excitatory neurotransmitter has not been assigned a role in chemoreception. To examine the possibility that glutamate and its N-methyl-d-aspartate (NMDA) receptors play a role in acclimatization after exposure to cyclic intermittent hypoxia (CIH), we exposed male Sprague-Dawley rats to cyclic hypoxia or to room air sham (Sham) for 8 h/day for 3 wk. Using RT-PCR, Western blot analysis, and immunohistochemistry, we found that ionotropic NMDA receptors, including NMDAR1, NMDAR2A, NMDAR2A/2B, are strongly expressed in the carotid body and colocalize with tyrosine hydroxylase in glomus cells. CIH exposure enhanced the expression of NMDAR1 and NMDAR2A/2B but did not substantially change the level of NMDAR2A. We assessed in vivo carotid sinus nerve activity (CSNA) at baseline, in response to acute hypoxia, in response to infused NMDA, and in response to infused endothelin-1 (ET-1) with and without MK-801, an NMDA receptor blocker. Infusion of NMDA augmented CSNA in CIH rats (124.61 ± 2.64% of baseline) but not in sham-exposed rats. Administration of MK-801 did not alter baseline activity or response to acute hypoxia, in either CIH or sham animals but did reduce the effect of ET-1 infusion on CSNA (CSNA after ET-1 = 160.96 ± 8.05% of baseline; ET-1 after MK-801 = 118.56 ± 9.12%). We conclude that 3-wk CIH exposure increases expression of NMDA functional receptors in rats, suggesting glutamate and its receptors may play a role in hypoxic acclimatization to CIH.

scholarly journals Diazepam attenuates the effects of cocaine on locomotion, 50-kHz ultrasonic vocalizations and phasic dopamine release in the nucleus accumbens of rats

2020 ◽  
Author(s):  
William N. Sanchez ◽  
Jose A. Pochapski ◽  
Leticia F. Jessen ◽  
Marek Ellenberger ◽  
Rainer K. Schwarting ◽  
...  
Keyword(s):  
Locomotor Activity ◽  
Nucleus Accumbens ◽  
Dopamine Release ◽  
Ultrasonic Vocalizations ◽  
Control Group ◽  
List Type ◽  
Adult Rats ◽  
Fast Scan Cyclic Voltammetry ◽  
Entire Duration ◽  
Male Wistar Rats

AbstractBackground and PurposeCurrently, no effective drug exists to treat cocaine use disorders, which affect millions of people worldwide. Benzodiazepines are potential therapeutic candidates, as microdialysis and voltammetry studies have shown that they can decrease dopamine release in the nucleus accumbens of rodents. In addition, we have recently shown that diazepam blocks the increase in dopamine release and the affective marker 50-kHz ultrasonic vocalizations (USV) induced by DL-amphetamine in rats.Experimental ApproachHere we tested whether administration of 2.5 mg·kg−1 diazepam (i.p.) in adult male Wistar rats could block the effects of 20 mg·kg−1 cocaine (i.p.) on electrically evoked phasic dopamine release in the nucleus accumbens measured by fast-scan cyclic voltammetry, as well as 50-kHz USV and locomotor activity.Key ResultsCocaine injection increased evoked dopamine release up to 3-fold within 5 min and the increase was significantly higher than baseline for at least 90 min. The injection of diazepam 15 min later attenuated the cocaine effect by nearly 50% and this attenuation was maintained for at least 30 min. Stimulant drugs, natural rewards and reward predictive cues are known to evoke 50-kHz USV in adult rats. In the present study, cocaine increased the number of 50-kHz USV of the flat, step, trill, and mixed kinds by 12-fold. This effect was at maximum 5 min after cocaine injection, decreased with time and lasted at least 40 min. Diazepam significantly blocked this effect for the entire duration of the session. The distance travelled by control rats during a 40-min session of exploration in an open field was at maximum in the first 5 min and decayed progressively until the end of the session. Cocaine-treated rats travelled significantly longer distances when compared to the control group, while diazepam significantly attenuated cocaine-induced locomotion by up to 50%.Conclusions and implicationThese results suggest that the neurochemical, affective, and stimulant effects of cocaine can be mitigated by diazepam.What is already knownDiazepam decreases dopamine release in the rodent nucleus accumbens (NAc) and reduces some effects produced by DL-amphetamine.What this study addsDiazepam attenuated the increase in phasic dopamine release caused by cocaine.Diazepam blocked the effect of cocaine on 50-kHz USV and locomotor activity.Clinical significanceThis study demonstrates that diazepam can block specific effects of cocaine that likely contribute to addiction.

scholarly journals The Effects of Exposure to Mephedrone During Adolescence on Brain Neurotransmission and Neurotoxicity in Adult Rats

2018 ◽  
Vol 34 (3) ◽  
pp. 525-537 ◽  
Author(s):  
Katarzyna Kamińska ◽  
Karolina Noworyta-Sokołowska ◽  
Anna Górska ◽  
Joanna Rzemieniec ◽  
Agnieszka Wnuk ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Glutamate Release ◽  
Cortical Cell ◽  
Synaptic Cleft ◽  
In Vivo Microdialysis ◽  
Male Rats ◽  
Adolescent Male ◽  
Turnover Rates ◽  
Adult Rats

Abstract According to the European Drug Report (2016), the use of synthetic cathinones, such as mephedrone, among young people has rapidly increased in the last years. Studies in humans indicate that psychostimulant drug use in adolescence increases risk of drug abuse in adulthood. Mephedrone by its interaction with transporters for dopamine (DAT) and serotonin (SERT) stimulates their release to the synaptic cleft. In animal studies, high repeated doses of mephedrone given to adolescent but not adult mice or rats induced toxic changes in 5-hydroxytryptamine (5-HT) neurons. The aim of our study was to investigate the effects of mephedrone given in adolescence on brain neurotransmission and possible neuronal injury in adult rats. Adolescent male rats were given mephedrone (5 mg/kg) for 8 days. In vivo microdialysis in adult rats showed an increase in dopamine (DA), 5-HT, and glutamate release in the nucleus accumbens and frontal cortex but not in the striatum in response to challenge dose in animals pretreated with mephedrone in adolescence. The 5-HT and 5-hydroxyindoleacetic acid contents decreased in the striatum and nucleus accumbens while DA turnover rates were decreased in the striatum and nucleus accumbens. The oxidative damage of DNA assessed with the alkaline comet assay was found in the cortex of adult rats. Therefore, the administration of repeated low doses of mephedrone during adolescence does not seem to induce injury to 5-HT and DA neurons. The oxidative stress seems to be responsible for possible damage of cortical cell bodies which causes maladaptive changes in serotonergic and dopaminergic neurons.

Modulation of [3H]MK-801 binding to NMDA receptors in vivo and in vitro

2000 ◽  
Vol 397 (2-3) ◽  
pp. 263-270 ◽  
Author(s):  
Fraser Murray ◽  
Jeffrey Kennedy ◽  
Peter H Hutson ◽  
Jason Elliot ◽  
Ian Huscroft ◽  
...  
Keyword(s):  
Nmda Receptors ◽  
Mk 801

scholarly journals Differential effects of acute and repeated stress on hippocampus and amygdala inputs to the nucleus accumbens shell

2013 ◽  
Vol 16 (9) ◽  
pp. 2013-2025 ◽  
Author(s):  
Kathryn M. Gill ◽  
Anthony A. Grace
Keyword(s):  
Nucleus Accumbens ◽  
Basolateral Amygdala ◽  
Acute Stress ◽  
Evoked Responses ◽  
Nucleus Accumbens Shell ◽  
Afferent Pathways ◽  
Repeated Stress ◽  
Repeated Restraint Stress ◽  
The Impact

Abstract The basolateral amygdala (BLA) and ventral subiculum (vSub) of the hippocampus convey emotion and context information, respectively, to the nucleus accumbens (NAc). Using in vivo extracellular recordings from NAc neurons, we examined how acute and repeated restraint stress alters the plasticity of the vSub and BLA afferent pathways. High-frequency (HFS) and low-frequency (LFS) stimulation was applied to the vSub to assess the impact on NAc responses to vSub and BLA inputs. In addition, iontophoretic application of the dopamine D2-antagonist sulpiride was used to explore the role of dopamine in the NAc in mediating the effects of stress on plasticity. Acute and repeated restraint caused disparate effects on BLA- and vSub-evoked responses in the NAc. Following repeated restraint, but not after acute restraint, HFS of the vSub failed to potentiate the vSub–NAc pathway while instead promoting a long-lasting reduction of the BLA–NAc pathway and these effects were independent of D2-receptor activity. In contrast, LFS to the vSub pathway after acute restraint resulted in potentiation in the vSub–NAc pathway while BLA-evoked responses were unchanged. When sulpiride was applied prior to LFS of the vSub after acute stress, there was a pronounced decrease in vSub-evoked responses similar to control animals. This work provides new insight into the impact of acute and repeated stress on the integration of context and emotion inputs in the NAc. These data support a model of stress whereby the hippocampus is inappropriately activated and dominates the information processing within this circuit via a dopaminergic mechanism after acute bouts of stress.

Modulation of locomotor activity by NMDA receptors in the nucleus accumbens core and shell regions of the rat

1994 ◽  
Vol 664 (1-2) ◽  
pp. 231-236 ◽  
Author(s):  
Luigi Pulvirenti ◽  
Renate Berrier ◽  
Max Kreifeldt ◽  
George K. Koob
Keyword(s):  
Locomotor Activity ◽  
Nucleus Accumbens ◽  
Nmda Receptors ◽  
Nucleus Accumbens Core ◽  
Accumbens Core
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