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 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 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.

scholarly journals Neurobehavioral and Ultrastructural Changes Induced by Phytosynthesized Silver-Nanoparticle Toxicity in an In Vivo Rat Model

Nanomaterials ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 58
Author(s):  
Razvan Vlad Opris ◽  
Vlad Toma ◽  
Alina Mihaela Baciu ◽  
Remus Moldovan ◽  
Bogdan Dume ◽  
...  
Keyword(s):  
Brain Regions ◽  
Time Dependent ◽  
Ultrastructural Changes ◽  
Control Group ◽  
Adult Rats ◽  
Male Adult ◽  
Cornus Mas ◽  
Transmission Electron ◽  
Altered Cell

(1) Background: The study aimed to assess neurobehavioral, ultrastructural, and biochemical changes induced by silver nanoparticles synthesized with Cornus mas L. extract (AgNPs-CM) in rat brains. (2) Methods: The study included 36 male adult rats divided into three groups. Over a period of 45 days, AgNPs-CM (0.8 and 1.5 mg/kg b.w.) were administered daily by gavage to two of the groups, while the control group received the vehicle used for AgNP. After treatment, OFT and EPM tests were conducted in order to assess neurobehavioral changes. Six of the animals from each group were sacrificed immediately after completion of treatment, while the remaining six were allowed to recuperate for an additional 15 days. Transmission electron microscopy (TEM), GFAP immunohistochemistry, and evaluation of TNFα, IL-6, MDA, and CAT activity were performed on the frontal cortex and hippocampus. (3) Results: Treated animals displayed a dose- and time-dependent increase in anxiety-like behavior and severe ultrastructural changes in neurons, astrocytes, and capillaries in both brain regions. Immunohistochemistry displayed astrogliosis with altered cell morphology. TNFα, IL-6, MDA, and CAT activity were significantly altered, depending on brain region and time post exposure. (4) Conclusions: AgNPs-CM induced neurobehavioral changes and severe cell lesions that continued to escalate after cessation of exposure.

Hyperlocomotion during Recovery from Isoflurane Anesthesia Is Associated with Increased Dopamine Turnover in the Nucleus Accumbens and Striatum in Mice

1997 ◽  
Vol 86 (2) ◽  
pp. 464-475 ◽  
Author(s):  
Masahiro Irifune ◽  
Tomoaki Sato ◽  
Takashige Nishikawa ◽  
Takashi Masuyama ◽  
Masahiro Nomoto ◽  
...  
Keyword(s):  
Locomotor Activity ◽  
Nucleus Accumbens ◽  
High Performance ◽  
Gas Flow ◽  
Brain Regions ◽  
Dopamine Neurons ◽  
Dopamine Turnover

Background It was recently reported that isoflurane increases dopamine release in the striatum in rats both in vivo and in vitro, and that isoflurane inhibits uptake of dopamine in the rat brain synaptosomes. However, the functional role of these effects of isoflurane on dopamine neurons is uncertain. Dopaminergic mechanisms within the nucleus accumbens and striatum play an important role in the control of locomotor activity, and a change in dopamine turnover depends essentially on a change in impulse flow in the dopamine neurons. In this study, the effects of isoflurane on locomotor activity and on dopamine turnover were investigated in discrete brain regions in mice. Methods Mice were placed in individual airtight clear plastic chambers and spontaneously breathed isoflurane in 25% oxygen and 75% nitrogen (fresh gas flow, 4 l/min). Locomotor activity was measured with an Animex activity meter. Animals were decapitated after treatments with or without isoflurane, and the concentrations of monoamines and their metabolites in different brain areas were measured by high-performance liquid chromatography. Results During the 10 min after the cessation of the 20-min exposure to isoflurane, there was a significant increase in locomotor activity in animals breathing 1.5% isoflurane but not 0.7% isoflurane. This increase in locomotor activity produced by 1.5% isoflurane was abolished by a low dose of haloperidol (0.1 mg/kg), a dopamine receptor antagonist. Regional brain monoamine assays revealed that 1.5% isoflurane significantly increased the 3,4-dihydroxyphenylacetic acid:dopamine ratio (one indicator of transmitter turnover) in the nucleus accumbens and striatum, but a concentration of 0.7% did not. This significant increase in dopamine turnover in these regions continued during 20 min after the cessation of the administration of 1.5% isoflurane. Conclusions These results suggest that isoflurane-induced hyperlocomotion during emergence may be associated with increased dopamine turnover in the nucleus accumbens and striatum.

scholarly journals Role of Dopaminergic System in Core Part of Nucleus Accumbens in Hyperlocomotion and Rearing Induced by MK-801 in Rats: A Behavioral and In Vivo Microdialysis Study

2001 ◽  
Vol 87 (4) ◽  
pp. 277-287 ◽  
Author(s):  
Izzettin Khatib ◽  
Funda Bölükbasi ◽  
Kenichi Mishima ◽  
Nobuaki Egashira ◽  
Katsunori Iwasaki ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Dopaminergic System ◽  
In Vivo Microdialysis ◽  
Mk 801 ◽  
Microdialysis Study ◽  
Core Part

scholarly journals Prolonged Membrane Potential Depolarization in Cingulate Pyramidal Cells after Digit Amputation in Adult Rats

2005 ◽  
Vol 1 ◽  
pp. 1744-8069-1-23 ◽  
Author(s):  
MF Wu ◽  
ZP Pang ◽  
M Zhuo ◽  
ZC Xu
Keyword(s):  
Membrane Potential ◽  
Pyramidal Neurons ◽  
Pyramidal Cells ◽  
Long Term Potentiation ◽  
Nmda Receptor Antagonist ◽  
Anterior Cingulate ◽  
Phantom Pain ◽  
Adult Rats ◽  
Brain Functions

The anterior cingulate cortex (ACC) plays an important role in higher brain functions including learning, memory, and persistent pain. Long-term potentiation of excitatory synaptic transmission has been observed in the ACC after digit amputation, which might contribute to plastic changes associated with the phantom pain. Here we report a long-lasting membrane potential depolarization in ACC neurons of adult rats after digit amputation in vivo. Shortly after digit amputation of the hind paw, the membrane potential of intracellularly recorded ACC neurons quickly depolarized from ∼−70 mV to ∼−15 mV and then slowly repolarized. The duration of this amputation-induced depolarization was about 40 min. Intracellular staining revealed that these neurons were pyramidal neurons in the ACC. The depolarization is activity-dependent, since peripheral application of lidocaine significantly reduced it. Furthermore, the depolarization was significantly reduced by a NMDA receptor antagonist MK-801. Our results provide direct in vivo electrophysiological evidence that ACC pyramidal cells undergo rapid and prolonged depolarization after digit amputation, and the amputation-induced depolarization in ACC neurons might be associated with the synaptic mechanisms for phantom pain.

scholarly journals Comparison of Cannabinoid CB1 Receptor Binding in Adolescent and Adult Rats: A Positron Emission Tomography Study Using [18F]MK-9470

2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
Mathieu Verdurand ◽  
Vu Nguyen ◽  
Daniela Stark ◽  
David Zahra ◽  
Marie-Claude Gregoire ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Brain Regions ◽  
Analysis Of Covariance ◽  
Emission Tomography ◽  
Adult Rats ◽  
Positron Emission ◽  
Marginal Means

Despite the important role of cannabinoid CB1 receptors (CB1R) in brain development, little is known about their status during adolescence, a critical period for both the development of psychosis and for initiation to substance abuse. In the present study, we assessed the ontogeny of CB1R in adolescent and adult rats in vivo using positron emission tomography with [18F]MK-9470. Analysis of covariance (ANCOVA) to control for body weight that would potentially influence [18F]MK-9470 values between the two groups revealed a main effect of age (F(1,109)=5.0, P=0.02) on [18F]MK-9470 absolute binding (calculated as percentage of injected dose) with adult estimated marginal means being higher compared to adolescents amongst 11 brain regions. This finding was confirmed using in vitro autoradiography with [3H]CP55,940 (F(10,99)=140.1, P<0.0001). This ontogenetic pattern, suggesting increase of CB1R during the transition from adolescence to adulthood, is the opposite of most other neuroreceptor systems undergoing pruning during this period.

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