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.

scholarly journals Attenuated dopamine receptor signaling in nucleus accumbens core in a rat model of chemically-induced neuropathy

2020 ◽  
Vol 166 ◽  
pp. 107935 ◽  
Author(s):  
Dana E. Selley ◽  
Matthew F. Lazenka ◽  
Laura J. Sim-Selley ◽  
Julie R. Secor McVoy ◽  
David N. Potter ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Dopamine Receptor ◽  
Rat Model ◽  
Receptor Signaling ◽  
Nucleus Accumbens Core ◽  
Chemically Induced ◽  
Accumbens Core

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 The nucleus accumbens core is necessary to scale fear to degree of threat

2020 ◽  
Author(s):  
Madelyn H. Ray ◽  
Alyssa N. Russ ◽  
Rachel A. Walker ◽  
Michael A. McDannald
Keyword(s):  
Nucleus Accumbens ◽  
Anxiety Disorders ◽  
Male Rats ◽  
Nucleus Accumbens Core ◽  
General Role ◽  
Discrimination Procedure ◽  
Neurotoxic Lesion ◽  
Long Evans ◽  
Rapid Discrimination ◽  
Accumbens Core

AbstractFear is adaptive when the level of the response rapidly scales to degree of threat. Using a discrimination procedure consisting of danger, uncertainty and safety cues, we have found rapid fear scaling (within two seconds of cue presentation) in male rats. Here we examined a possible role for the nucleus accumbens core (NAcc) in the acquisition and expression of fear scaling. In experiment 1, male Long Evans rats received bilateral sham or neurotoxic NAcc lesions, recovered and underwent fear discrimination. NAcc-lesioned rats were generally impaired in scaling fear to degree of threat, and specifically impaired in rapid uncertainty-safety discrimination. In experiment 2, male Long Evans rats received NAcc transduction with halorhodopsin or a control fluorophore. After fear scaling was established, the NAcc was illuminated during cue or control periods. NAcc-halorhodopsin rats receiving cue illumination were specifically impaired in rapid uncertainty-safety discrimination. The results reveal a general role for the NAcc in scaling fear to degree of threat, and a specific role in rapid discrimination of uncertain threat and safety.Significance StatementRapidly discriminating cues for threat and safety is essential for survival and impaired threat-safety discrimination is a hallmark of stress and anxiety disorders. In two experiments, we induced nucleus accumbens core (NAcc) dysfunction in rats receiving fear discrimination consisting of cues for danger, uncertainty and safety. Permanent NAcc dysfunction, via neurotoxic lesion, generally disrupted the ability to scale fear to degree of threat, and specifically impaired one component of scaling: rapid discrimination of uncertain threat and safety. Reversible NAcc dysfunction, via optogenetic inhibition, specifically impaired rapid discrimination of uncertain threat and safety. The results reveal that the NAcc is essential to scale fear to degree of threat, and is a plausible source of dysfunction in stress and anxiety disorders.

scholarly journals Olanzapine treatment of adolescent rats alters adult reward behaviour and nucleus accumbens function

2013 ◽  
Vol 16 (7) ◽  
pp. 1599-1609 ◽  
Author(s):  
Monika Vinish ◽  
Ahmed Elnabawi ◽  
Jean A. Milstein ◽  
Jesse S. Burke ◽  
Jonathan K. Kallevang ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Early Life ◽  
D1 Receptor ◽  
Male Rats ◽  
Adolescent Male ◽  
Long Term Effects ◽  
Nucleus Accumbens Core ◽  
Asymptomatic Patients ◽  
Adolescent Rats

Abstract Antipsychotic drugs are increasingly used in children and adolescents to treat a variety of psychiatric disorders. However, little is known about the long-term effects of early life antipsychotic drug (APD) treatment. Most APDs are potent antagonists or partial agonists of dopamine (DA) D2 receptors; atypical APDs also have multiple serotonergic activities. DA and serotonin regulate many neurodevelopmental processes. Thus, early life APD treatment can, potentially, perturb these processes, causing long-term behavioural and neurobiological sequelae. We treated adolescent, male rats with olanzapine (Ola) on post-natal days 28–49, under dosing conditions that approximate those employed therapeutically in humans. As adults, they exhibited enhanced conditioned place preference for amphetamine, as compared to vehicle-treated rats. In the nucleus accumbens core, DA D1 receptor binding was reduced, D2 binding was increased and DA release evoked by electrical stimulation of the ventral tegmental area was reduced. Thus, adolescent Ola treatment enduringly alters a key behavioural response to rewarding stimuli and modifies DAergic neurotransmission in the nucleus accumbens. The persistence of these changes suggests that even limited periods of early life Ola treatment may induce enduring changes in other reward-related behaviours and in behavioural and neurobiological responses to therapeutic and illicit psychotropic drugs. These results underscore the importance of improved understanding of the enduring sequelae of paediatric APD treatment as a basis for weighing the benefits and risks of adolescent APD therapy, especially prophylactic treatment in high-risk, asymptomatic patients.

Increased expression of cannabinoid receptor 1 in the nucleus accumbens core in a rat model with morphine withdrawal

2013 ◽  
Vol 1531 ◽  
pp. 102-112 ◽  
Author(s):  
Wei-Xin Yuan ◽  
Li-Jun Heng ◽  
Jie Ma ◽  
Xing-Qin Wang ◽  
Li-Juan Qu ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Rat Model ◽  
Cannabinoid Receptor ◽  
Morphine Withdrawal ◽  
Cannabinoid Receptor 1 ◽  
Nucleus Accumbens Core ◽  
Accumbens Core

scholarly journals Regulation of CREB Phosphorylation in Nucleus Accumbens after Relief Conditioning

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 238
Author(s):  
Elaheh Soleimanpour ◽  
Jorge R. Bergado Acosta ◽  
Peter Landgraf ◽  
Dana Mayer ◽  
Evelyn Dankert ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Dorsal Hippocampus ◽  
Dorsal Striatum ◽  
Brain Regions ◽  
D1 Receptor ◽  
Male Rats ◽  
Molecular Pathways ◽  
Western Blots ◽  
Creb Phosphorylation ◽  
Aversive Events

Relief learning is the association of environmental cues with the cessation of aversive events. While there is increasing knowledge about the neural circuitry mediating relief learning, the respective molecular pathways are not known. Therefore, the aim of the present study was to examine different putative molecular pathways underlying relief learning. To this purpose, male rats were subjected either to relief conditioning or to a pseudo conditioning procedure. Forty-five minutes or 6 h after conditioning, samples of five different brain regions, namely the prefrontal cortex, nucleus accumbens (NAC), dorsal striatum, dorsal hippocampus, and amygdala, were collected. Using quantitative Western blots, the expression level of CREB, pCREB, ERK1/2, pERK1/2, CaMKIIα, MAP2K, PKA, pPKA, Akt, pAkt, DARPP-32, pDARPP-32, 14-3-3, and neuroligin2 were studied. Our analyses revealed that relief conditioned rats had higher CREB phosphorylation in NAC 6 h after conditioning than pseudo conditioned rats. The data further revealed that this CREB phosphorylation was mainly induced by dopamine D1 receptor-mediated activation of PKA, however, other kinases, downstream of the NMDA receptor, may also contribute. Taken together, the present study suggests that CREB phosphorylation, induced by a combination of different molecular pathways downstream of dopamine D1 and NMDA receptors, is essential for the acquisition and consolidation of relief learning.

scholarly journals Role of prefrontal cortex projections to the nucleus accumbens core in mediating the effects of ceftriaxone on cued cocaine relapse

2020 ◽  
Author(s):  
Allison R. Bechard ◽  
Carly N. Logan ◽  
Javier Mesa ◽  
Yasmin Padovan Hernandez ◽  
Harrison Blount ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Nucleus Accumbens ◽  
Basolateral Amygdala ◽  
Male Rats ◽  
Self Administration ◽  
Nucleus Accumbens Core ◽  
Cocaine Seeking ◽  
Context Cues ◽  
Glutamate Efflux

AbstractCeftriaxone is an antibiotic that reliably attenuates the reinstatement of cocaine-seeking after extinction while preventing the nucleus accumbens (NA) core glutamate efflux that drives reinstatement. However, when rats undergo abstinence without extinction, ceftriaxone attenuates context-primed relapse but NA core glutamate efflux still increases. Here we sought to determine if the same would occur when relapse is prompted by both context and discrete cues (context+cues) after cocaine abstinence. Male rats self-administered intravenous cocaine for 2 hr/day for 2 weeks. Cocaine delivery was accompanied by drug-associated cues (light+tone). Rats were then placed into abstinence with daily handling but no extinction training for two weeks. Ceftriaxone (200 mg/kg IP) or vehicle was administered during the last 6 days of abstinence. During a context+cue relapse test, microdialysis procedures were conducted. Rats were perfused at the end of the test for later Fos analysis. A separate cohort of rats was infused with the retrograde tracer cholera toxin B in the NA core and underwent the same self-administration and relapse procedures. Ceftriaxone increased baseline glutamate and attenuated both context+cue-primed relapse and NA core glutamate efflux during this test. Ceftriaxone reduced Fos expression in regions sending projections to the NA core (prefrontal cortex, basolateral amygdala, ventral tegmental area) and specifically reduced Fos in prelimbic cortex and not infralimbic cortex neurons projecting to the NA core. Thus, when relapse is primed by drug-associated cues and context, ceftriaxone is able to attenuate relapse by preventing NA core glutamate efflux, likely through reducing activity in prelimbic NA core-projecting neurons.

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