scholarly journals Effects of high dosage methamphetamine on glutamatergic neurotransmission in the nucleus accumbens and prefrontal cortex.

2021 ◽  
Author(s):  
Devesh Mishra ◽  
Jose I. Pena-Bravo ◽  
Shannon M. Ghee ◽  
Carole Berini ◽  
Carmela M. Reichel ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Nucleus Accumbens ◽  
Brain Regions ◽  
High Dose ◽  
Glutamatergic Neurotransmission ◽  
Glutamatergic Transmission ◽  
Nucleus Accumbens Core ◽  
Dopaminergic Transmission ◽  
Field Recordings ◽  
Medial Pfc

Rationale: Methamphetamine (METH) induces changes in the glutamatergic system and elicits cellular alterations in the cortico-accumbens circuit. Objective: While there is a body of literature on the effects of METH on dopaminergic transmission, there is a gap in knowledge regarding the effects of a high dose of METH on synaptic glutamatergic neurotransmission, specifically in brain regions involved in goal directed behavior (nucleus accumbens core; NAc core) and executive functions (prefrontal cortex;PFC). Methods: In order to fill that gap we assessed synaptic glutamatergic transmission using a well established METH administration regime (4 x 4 mg/kg ip at 2 hr intervals) followed by 7 days of abstinence. Rats were then sacrificed and whole cell and field recordings were performed in the NAc core and medial PFC. Results: METH treatment elicited a significant decrease in paired pulse ratio in NAc core and a significant increase in AMPA/NMDA ratio driven by increases in AMPA currents. On the other hand, there were no significant changes in measures of synaptic glutamate in the PFC. Conclusion: These results suggest that a high dose of METH treatment followed by a period of abstinence elicits significant increases in indices of glutamatergic transmission in the NAc core with no detectable changes in mPFC, denoting that neurons and glutamate terminals in this limbic region have a higher susceptibility to a neurotoxic METH regime.

scholarly journals Role of prefrontal cortex projections to the nucleus accumbens core in mediating the effects of ceftriaxone on cue‐induced cocaine seeking

2020 ◽  
Author(s):  
Allison R. Bechard ◽  
Carly N. Logan ◽  
Javier Mesa ◽  
Yasmin Padovan‐Hernandez ◽  
Harrison Blount ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Nucleus Accumbens ◽  
Nucleus Accumbens Core ◽  
Cocaine Seeking ◽  
Accumbens Core

scholarly journals Expression of Dopamine-Related Genes in Four Human Brain Regions

2020 ◽  
Vol 10 (8) ◽  
pp. 567
Author(s):  
Ansley Grimes Stanfill ◽  
Xueyuan Cao
Keyword(s):  
Prefrontal Cortex ◽  
Nucleus Accumbens ◽  
Substantia Nigra ◽  
Human Brain ◽  
Demographic Characteristic ◽  
Treatment Options ◽  
Tissue Expression ◽  
Brain Regions ◽  
Future Treatment ◽  
Psychiatric Conditions

A better understanding of dopaminergic gene expression will inform future treatment options for many different neurologic and psychiatric conditions. Here, we utilized the National Institutes of Health’s Genotype-Tissue Expression project (GTEx) dataset to investigate genotype by expression associations in seven dopamine pathway genes (ANKK1, DBH, DRD1, DRD2, DRD3, DRD5, and SLC6A3) in and across four human brain tissues (prefrontal cortex, nucleus accumbens, substantia nigra, and hippocampus). We found that age alters expression of DRD1 in the nucleus accumbens and prefrontal cortex, DRD3 in the nucleus accumbens, and DRD5 in the hippocampus and prefrontal cortex. Sex was associated with expression of DRD5 in substantia nigra and hippocampus, and SLC6A3 in substantia nigra. We found that three linkage disequilibrium blocks of SNPs, all located in DRD2, were associated with alterations in expression across all four tissues. These demographic characteristic associations and these variants should be further investigated for use in screening, diagnosis, and future treatment of neurological and psychiatric conditions.

2Hz-Electroacupuncture Attenuates Conditioned Cue-Evoked Heroin-Seeking Behavior and Increase CB2-Rs Expression in Relapse-Relevant Brain Regions in Heroin-Addicted Rats

2014 ◽  
Vol 998-999 ◽  
pp. 164-168 ◽  
Author(s):  
Lin Chen ◽  
Bao Miao Ma ◽  
Kai Yue ◽  
Qin Ru ◽  
Xiang Tian ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Nucleus Accumbens ◽  
Rat Model ◽  
Fixed Ratio ◽  
Brain Regions ◽  
Inhibitory Effect ◽  
Control Group ◽  
Self Administration ◽  
Seeking Behavior

In order to investigate the influence of electroacupuncture on heroin seeking behavior and the expression of CB2-Rs in the relapse-relevant brain regions, heroin self-administration rat model which represents the heroin relapse behaviors was developed with progressive fixed ratio program. The model rats were randomly divided into 3 groups: control group, heroin-addicted group and 2Hz electroacupuncture group (stimulating on acupoints zusanli and sanyinjiao). The expression of CB2-Rs in the relapse-relevant brain regions were assessed with immunohistochemistry technologies. The reinstatement of heroin seeking behavior induced by conditioned cue priming showed that compared with the heroin-addicted group, active pokes in the 2Hz electroacupuncture group decreased significantly (p<0.05). Compared with the control group, the expression of CB2-Rs in prefrontal cortex (PFC) and nucleus accumbens (NAc) was significantly decreased (p<0.05) in heroin-addicted group and increaseed significantly recover (p<0.05) in the 2Hz electroacupuncture group. Our present results showed that 2Hz-electroacupuncture could attenuate the conditioned cue-evoked heroin-seeking behavior and the inhibitory effect was mediated partially by the increase CB2-Rs expression in relapse-relevant brain regions in heroin-addicted rats.

scholarly journals Role of the medial prefrontal cortex and nucleus accumbens in an operant model of checking behaviour and uncertainty

2017 ◽  
Vol 1 ◽  
pp. 239821281773340 ◽  
Author(s):  
Camilla d’Angelo ◽  
Dawn M. Eagle ◽  
Cristina-M. Coman ◽  
Trevor W. Robbins
Keyword(s):  
Prefrontal Cortex ◽  
Nucleus Accumbens ◽  
Obsessive Compulsive Disorder ◽  
Medial Prefrontal Cortex ◽  
Nucleus Accumbens Core ◽  
Obsessive Compulsive ◽  
Compulsive Disorder ◽  
Observing Response ◽  
Response Task ◽  
Accumbens Core

Background: Excessive checking is a common, debilitating symptom of obsessive–compulsive disorder. To further examine cognitive processes underpinning checking behaviour, and clarify how and why checking develops, we designed a novel operant paradigm for rats, the observing response task. The present study used the observing response task to investigate checking behaviour following excitotoxic lesions of the medial prefrontal cortex, nucleus accumbens core and dorsal striatum, brain regions considered to be of relevance to obsessive–compulsive disorder. Methods: In the observing response task, rats pressed an ‘observing’ lever for information (provided by light onset) about the location of an ‘active’ lever that provided food reinforcement. Following training, rats received excitotoxic lesions of the regions described above and performance was evaluated post-operatively before histological processing. Results: Medial prefrontal cortex lesions selectively increased functional checking with a less-prominent effect on non-functional checking and reduced discrimination accuracy during light information periods. Rats with nucleus accumbens core lesions made significantly more checking responses than sham-lesioned rats, including both functional and non-functional checking. Dorsal striatum lesions had no direct effect on checking per se, but reduced both active and inactive lever presses, and therefore changed the relative balance between checking responses and instrumental responses. Conclusions: These results suggest that the medial prefrontal cortex and nucleus accumbens core are important in the control of checking, perhaps via their role in processing uncertainty of reinforcement, and that dysfunction of these regions may therefore promote excessive checking behaviour, possibly relevant to obsessive-compulsive disorder.

scholarly journals 2Hz-Electroacupuncture Attenuates Heroin-Seeking Behaviors via Adjusts CB1-Rs and CB2-Rs Expression in Relapse-Relevant Brain Regions of Heroin Self-Administration Rats

2019 ◽  
pp. 835-844
Author(s):  
L. CHEN ◽  
X.-K. GONG ◽  
C.-L. LENG ◽  
B.-M. MA ◽  
Q. RU ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Nucleus Accumbens ◽  
Ventral Tegmental Area ◽  
Brain Regions ◽  
High Rate ◽  
Opiate Addiction ◽  
Control Group ◽  
Self Administration ◽  
Ventral Tegmental

Opiate addiction has a high rate of relapse. The accumulating evidence shows that electroacupuncture (EA) may be effective for the treatment of opiate relapse. However, the change of expression of CB1-Rs and CB2-Rs involve in 2Hz EA anti-relapse pathway is still unclear. To explore the changes of expression of CB1-Rs and CB2-Rs, heroin self-administration (SA) model rats were adopted and treated using 2Hz EA. The expressions of CB1-Rs and CB2-Rs were observed using immunohistochemistry method. The results showed that, compared with the control group, active pokes in the heroin-addicted group increased, while the active pokes decreased significantly in 2Hz EA group compared with heroin-addicted group. Correspondingly, the expression of CB1-Rs in prefrontal cortex (PFC), hippocampus (Hip), nucleus accumbens (NAc) and ventral tegmental area (VTA) all increased significantly while the expression of CB2-Rs in those relapse-relevant brain regions decreased obviously in heroin-addicted group when compared with the control group. In addition, the expression of CB1-Rs obviously decreased in the 2Hz EA group while the expression of CB2-Rs in those relapse-relevant brain regions increased significantly when compared with the heroin-addicted group. It indicated that 2Hz EA could attenuate the heroin-evoked seeking behaviors effectively. The anti-relapse effects of 2Hz EA might be related to the decrease of CB1-Rs and increase of CB2-Rs expression in relapse-relevant brain regions of heroin SA rats.

scholarly journals Attenuated Dopamine Receptor Signaling in Nucleus Accumbens Core in a Rat Model of Chemically-Induced Neuropathy

2019 ◽  
Author(s):  
D.E. Selley ◽  
M.F. Lazenka ◽  
L.J. Sim-Selley ◽  
D. N. Potter ◽  
Elena H. Chartoff ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Dopamine Receptor ◽  
Rat Model ◽  
Brain Regions ◽  
Male Rats ◽  
Formalin Injection ◽  
Receptor Signaling ◽  
Nucleus Accumbens Core ◽  
Protein Activation ◽  
Chemically Induced

ABSTRACTNeuropathy is major source of chronic pain that can be caused by mechanically or chemically induced nerve injury. Previous work in a rat model of neuropathic pain demonstrated that bilateral formalin injection into the hind paws produced mechanical hypersensitivity (allodynia) and depressed responding for intracranial self-stimulation (ICSS). To determine whether neuropathy alters dopamine receptor responsiveness in mesolimbic brain regions, we examined dopamine D1-like and D2-like receptor (D1/2R) signaling and expression in male rats 14 days after bilateral intraplantar formalin injections into both rear paws. D2R-mediated G-protein activation and expression of the D2R long, but not short, isoform were reduced in nucleus accumbens (NAc) core, but not in NAc shell, caudate-putamen (CPu) or ventral tegmental area (VTA) of formalin-compared to saline-treated rats. In addition, D1R-stimulated adenylyl cyclase (AC) activity was also reduced in NAc core, but not in NAc shell or prefrontal cortex, of formalin-treated rats, whereas D1R expression was unaffected. Expression of other proteins involved in dopamine neurotransmission, including dopamine uptake transporter (DAT) and tyrosine hydroxylase (TH), were unaffected by formalin treatment. In behavioral tests, the effects of D2R agonists on ICSS were attenuated in formalin-treated rats, whereas the effects of D1R agonists were unchanged. These results indicate that intraplantar formalin as a model of chemically induced neuropathy produces attenuation of highly specific DA receptor signaling processes in NAc core of male rats.

Circadian disruption in mice through chronic jetlag-like conditions modulates molecular profiles of cancer in nucleus accumbens and prefrontal cortex

2021 ◽  
Author(s):  
Suliman Khan ◽  
V Wee Yong ◽  
Mengzhou Xue
Keyword(s):  
Prefrontal Cortex ◽  
Nucleus Accumbens ◽  
Pet Imaging ◽  
Biological Rhythms ◽  
Brain Regions ◽  
Molecular Signature ◽  
Environmental Light ◽  
Positron Emission ◽  
The Individual ◽  
Risk Of Cancer

Abstract Biological rhythms regulate physiological activities. Shiftwork disrupts normal circadian rhythms and may increase the risk of cancer through unknown mechanisms. To mimic environmental light/dark changes encountered by shift workers, a protocol called “chronic jet lag (CJL)” induced by repeatedly shifting light-dark cycles has been used. Here, we subjected mice to CJL by advancing light–dark cycle by 6 hours every 2 days, and conducted RNA sequencing to analyze the expression profile and molecular signature in the brain areas of prefrontal cortex and nucleus accumbens. We also performed positron emission tomography (PET) imaging to monitor changes related to glucose metabolism in brain. Our results reveal systematic reprogramming of gene expression associated with cancer related pathways and metabolic pathways in prefrontal cortex and nucleus accumbens. PET imaging indicates that glucose uptake level was significantly reduced in whole brain as well as the individual brain regions. Moreover, qPCR analysis describes that the expression levels of cancer related genes were altered in prefrontal cortex and nucleus accumbens. Overall, these results suggest a molecular and metabolic link with CJL mediated cancer risk, and generate hypotheses on how CJL increases the susceptibility to cancer.

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