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 Microarray analysis reveals distinctive signaling between the bed nucleus of the stria terminalis, nucleus accumbens, and dorsal striatum

2008 ◽  
Vol 32 (3) ◽  
pp. 283-298 ◽  
Author(s):  
Christopher M. Olsen ◽  
Yong Huang ◽  
Shirlean Goodwin ◽  
Daniel C. Ciobanu ◽  
Lu Lu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Synaptic Plasticity ◽  
Nucleus Accumbens ◽  
Signaling Pathways ◽  
Microarray Analysis ◽  
Dorsal Striatum ◽  
Brain Regions ◽  
Stria Terminalis ◽  
Bed Nucleus ◽  
Insight Into

To identify distinct transcriptional patterns between the major subcortical dopamine targets commonly studied in addiction we studied differences in gene expression between the bed nucleus of the stria terminalis (BNST), nucleus accumbens (NAc), and dorsal striatum (dStr) using microarray analysis. We first tested for differences in expression of genes encoding transcripts for common neurotransmitter systems as well as calcium binding proteins routinely used in neuroanatomical delineation of brain regions. This a priori method revealed differential expression of corticotropin releasing hormone ( Crh), the GABA transporter ( Slc6a1), and prodynorphin ( Pdyn) mRNAs as well as several others. Using a gene ontology tool, functional scoring analysis, and Ingenuity Pathway Analysis, we further identified several physiological pathways that were distinct among these brain regions. These two different analyses both identified calcium signaling, G-coupled protein receptor signaling, and adenylate cyclase-related signaling as significantly different among the BNST, NAc, and dStr. These types of signaling pathways play important roles in, amongst other things, synaptic plasticity. Investigation of differential gene expression revealed several instances that may provide insight into reported differences in synaptic plasticity between these brain regions. The results support other studies suggesting that crucial pathways involved in neurotransmission are distinct among the BNST, NAc, and dStr and provide insight into the potential use of pharmacological agents that may target region-specific signaling pathways. Furthermore, these studies provide a framework for future mouse-mouse comparisons of transcriptional profiles after behavioral/pharmacological manipulation.

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 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.

scholarly journals Dopamine D1 receptor signalling in the lateral shell of the nucleus accumbens controls dietary fat intake in male rats

Appetite ◽  
2021 ◽  
pp. 105597
Author(s):  
Anil Joshi ◽  
Tess Kool ◽  
Charlene Diepenbroek ◽  
Laura L. Koekkoek ◽  
Leslie Eggels ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Dietary Fat ◽  
Dopamine D1 Receptor ◽  
D1 Receptor ◽  
Male Rats ◽  
Fat Intake ◽  
Receptor Signalling ◽  
Dietary Fat Intake

scholarly journals Exposure to the predator odor TMT induces early and late differential gene expression related to stress and excitatory synaptic function throughout the brain in male rats

2020 ◽  
Author(s):  
Ryan E. Tyler ◽  
Ben Weinberg ◽  
Dennis Lovelock ◽  
Laura Ornelas ◽  
Joyce Besheer
Keyword(s):  
Gene Expression ◽  
Nucleus Accumbens ◽  
Dorsal Hippocampus ◽  
Synaptic Function ◽  
Predator Odor ◽  
Male Rats ◽  
Prelimbic Cortex ◽  
Post Traumatic Stress ◽  
Early Stress ◽  
Post Traumatic

AbstractPersistent changes in brain stress and glutamatergic function are associated with post-traumatic stress disorder (PTSD). Rodent exposure to the predator odor trimethylthiazoline (TMT) is an innate stressor that produces lasting behavioral consequences relevant to PTSD. As such, the goal of the present study was to assess early (6 hours and 2 days) and late (4 weeks) changes to gene expression (RT-PCR) related to stress and excitatory function following TMT exposure in male, Long-Evans rats. During TMT exposure, rats engaged in stress reactive behaviors, including digging and immobility. Further, the TMT group displayed enhanced exploration and mobility in the TMT-paired context one week after exposure, suggesting a lasting contextual reactivity. Gene expression analyses revealed upregulated FKBP5 6 hours post-TMT in the hypothalamus and dorsal hippocampus. Two days after TMT, GRM3 was downregulated in the prelimbic cortex and dorsal hippocampus, but upregulated in the nucleus accumbens. This may reflect an early stress response (FKBP5) that resulted in later glutamatergic adaptation (GRM3). Finally, four weeks after TMT exposure, several differentially expressed genes known to mediate excitatory tripartite synaptic function were observed. Specifically in the prelimbic cortex (GRM5, DLG4 and SLC1A3 upregulated), infralimbic cortex (GRM2 downregulated, Homer1 upregulated), nucleus accumbens (GRM7 and SLC1A3 downregulated), dorsal hippocampus (FKBP5 and NR3C2 upregulated, SHANK3 downregulated) and ventral hippocampus (CNR1, GRM7, GRM5, SHANK3, and Homer1 downregulated). These data demonstrate that TMT exposure stress induces early and late stress and excitatory molecular adaptations, which may help us understand the persistent glutamatergic dysfunction observed in PTSD.

scholarly journals Pyk2 in D1 receptor-expressing neurons of the nucleus accumbens modulates the acute locomotor effects of cocaine

2019 ◽  
Author(s):  
Benoit de Pins ◽  
Enrica Montalban ◽  
Peter Vanhoutte ◽  
Albert Giralt ◽  
Jean-Antoine Girault
Keyword(s):  
Nucleus Accumbens ◽  
Protein Tyrosine Kinase ◽  
Drugs Of Abuse ◽  
Anticholinergic Drug ◽  
Dorsal Striatum ◽  
D1 Receptor ◽  
Locomotor Sensitization ◽  
Locomotor Response ◽  
Erk Phosphorylation

AbstractThe striatum is a critical brain region for locomotor response to cocaine. Although the D1 receptor-expressing neurons are centrally involved in mediating the locomotor effects of cocaine, the molecular pathways controlling this response are not fully understood. Here we studied the role of Pyk2, a non-receptor calcium-dependent protein-tyrosine kinase, in striatum-related functions. We discovered that cocaine injection increases Pyk2 phosphorylation in the striatum of mice in vivo. Pyk2-deficient mice displayed an altered locomotor response to acute cocaine injection. In contrast, they developed normal locomotor sensitization and cocaine-conditioned place preference. Accordingly, a cocaine-activated signaling pathway essential for these late responses, ERK phosphorylation, was not altered. Specific deletion of Pyk2 in the nucleus accumbens or in D1 neurons reproduced this phenotype, whereas deletion of Pyk2 in the dorsal striatum or in A2A receptor-expressing neurons did not. Mice lacking Pyk2 in D1-neurons also displayed lower locomotor response to the D1 receptor agonist SKF-81297 but not to an anticholinergic drug. Our results identify Pyk2 as a regulator of acute locomotor responses to psychostimulants and suggest that changes in Pyk2 expression or activation may alter specific responses to drugs of abuse, or possibly other behavioral responses linked to dopamine action.

Musical Anhedonia

2020 ◽  
Vol 31 (2) ◽  
pp. 62-68
Author(s):  
Sara E. Holm ◽  
Alexander Schmidt ◽  
Christoph J. Ploner
Keyword(s):  
Quality Of Life ◽  
Nucleus Accumbens ◽  
Brain Damage ◽  
Parietal Cortex ◽  
Neurological Disorders ◽  
Brain Regions ◽  
Precise Information ◽  
Exact Localization ◽  
High Prevalence

Abstract. Some people, although they are perfectly healthy and happy, cannot enjoy music. These individuals have musical anhedonia, a condition which can be congenital or may occur after focal brain damage. To date, only a few cases of acquired musical anhedonia have been reported in the literature with lesions of the temporo-parietal cortex being particularly important. Even less literature exists on congenital musical anhedonia, in which impaired connectivity of temporal brain regions with the Nucleus accumbens is implicated. Nonetheless, there is no precise information on the prevalence, causes or exact localization of both congenital and acquired musical anhedonia. However, the frequent involvement of temporo-parietal brain regions in neurological disorders such as stroke suggest the possibility of a high prevalence of this disorder, which leads to a considerable reduction in the quality of life.

Role of nucleus accumbens microRNA-181a and MeCP2 in incubation of heroin craving in male rats

2021 ◽  
Author(s):  
Wenjin Xu ◽  
Qingxiao Hong ◽  
Zi Lin ◽  
Hong Ma ◽  
Weisheng Chen ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Male Rats

scholarly journals A Guide to the Generation of a 6-Hydroxydopamine Mouse Model of Parkinson’s Disease for the Study of Non-Motor Symptoms

Biomedicines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 598
Author(s):  
Débora Masini ◽  
Carina Plewnia ◽  
Maëlle Bertho ◽  
Nicolas Scalbert ◽  
Vittorio Caggiano ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mouse Model ◽  
Survival Rates ◽  
Dorsal Striatum ◽  
Brain Regions ◽  
Motor Symptoms ◽  
Operative Care ◽  
6 Hydroxydopamine ◽  
Non Motor Symptoms

In Parkinson’s disease (PD), a large number of symptoms affecting the peripheral and central nervous system precede, develop in parallel to, the cardinal motor symptoms of the disease. The study of these conditions, which are often refractory to and may even be exacerbated by standard dopamine replacement therapies, relies on the availability of appropriate animal models. Previous work in rodents showed that injection of the neurotoxin 6-hydroxydopamine (6-OHDA) in discrete brain regions reproduces several non-motor comorbidities commonly associated with PD, including cognitive deficits, depression, anxiety, as well as disruption of olfactory discrimination and circadian rhythm. However, the use of 6-OHDA is frequently associated with significant post-surgical mortality. Here, we describe the generation of a mouse model of PD based on bilateral injection of 6-OHDA in the dorsal striatum. We show that the survival rates of males and females subjected to this lesion differ significantly, with a much higher mortality among males, and provide a protocol of enhanced pre- and post-operative care, which nearly eliminates animal loss. We also briefly discuss the utility of this model for the study of non-motor comorbidities of PD.

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