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David F Tate, Benjamin S C Wade, Carmen S Velez, Ann Marie Drennon, Jacob D Bolzenius, Douglas B Cooper, Jan E Kennedy, Matthew W Reid, Amy O Bowles, Paul M Thompson, Boris A Gutman, Jeffrey D Lewis, John L Ritter, Gerald E York, Erin D Bigler
In a recent manuscript, our group demonstrated shape differences in the thalamus, nucleus accumbens, and amygdala in a cohort of U.S. Service Members with mild traumatic brain injury (mTBI). Given the significant role these structures play in cognitive function, this study directly examined the relationship between shape metrics and neuropsychological performance. The imaging and neuropsychological data from 135 post-deployed United States Service Members from two groups (mTBI and orthopedic injured) were examined...
March 21, 2018: Brain Imaging and Behavior
Chunxiao Qi, Xiaoming Ji, Guoliang Zhang, Yunxiao Kang, Yuanxiang Huang, Rui Cui, Shuangcheng Li, Huixian Cui, Geming Shi
The purpose of present study was to infer the potential effects of testosterone increase in some male-based childhood-onset neuropsychiatric disorders, such as Tourette syndrome. Thus, the influence of early postnatal androgen exposure upon the neurobehaviors and its possible neural basis were investigated in the study. Male pup rats received consecutive 14-day testosterone propionate (TP) subcutaneous injection from postnatal day (PND) 7. The TP treatment produced the hyperactive motor behavior and grooming behavior as well as the increased levels of dopamine, tyrosine hydroxylase and dopamine transporter in the mesodopaminergic system and the elevated levels of serotonin in the nucleus accumbens, without affecting the levels of glutamate, γ-aminobutyric acid, norepinephrine and histamine in the caudate putamen and nucleus accumbens of PND21 and PND49 rats...
March 21, 2018: Journal of Endocrinology
Jacob Itzhacki, Daniel Clesse, Yannick Goumon, Eus J Van Someren, Jorge Mendoza
Seasonal affective disorder (SAD), beyond mood changes, is characterized by alterations in daily rhythms of behavior and physiology. The pathophysiological conditions of SAD involve changes in day length and its first-line treatment is bright light therapy. Animal models using nocturnal rodents have been studied to elucidate the neurobiological mechanisms of depression, but might be ill suited to study the therapeutic effects of light in SAD since they exhibit light-aversive responses. Here Arvicanthis ansorgei, a diurnal rodent, was used to determine behavioral, molecular and brain dopamine changes in response to exposure to a winter-like photoperiod consisting of a light-dark cycle with 8 h of light, under diminished light intensity, and 16 h of darkness...
March 20, 2018: Brain Structure & Function
Lisanne M Jenkins, Kristy A Skerrett, Sophie R DelDonno, Víctor G Patrón, Kortni K Meyers, Scott Peltier, Jon-Kar Zubieta, Scott A Langenecker, Monica N Starkman
We investigated the ability of preferred classical music to activate the nucleus accumbens in patients with Major depressive disorder (MDD). Twelve males with MDD and 10 never mentally ill male healthy controls (HC) completed measures of anhedonia and depression severity, and listened to 90-second segments of preferred classical music during fMRI. Compared to HCs, individuals with MDD showed less activation of the left nucleus accumbens (NAcc). Individuals with MDD showed attenuation of the left NAcc response in later compared to earlier parts of the experiment, supporting theories that MDD involves an inability to sustain reward network activation...
March 5, 2018: Psychiatry Research
Rebecca L Barlow, Martin Gorges, Alfie Wearn, Heiko G Niessen, Jan Kassubek, Jeffrey W Dalley, Anton Pekcec
Background: Low dopamine D2/3 receptor availability in the nucleus accumbens (NAcb) shell is associated with highly-impulsive behavior in rats, as measured by premature responses in a cued attentional task. However, it is unclear whether dopamine D2/3 receptor availability in the NAcb is equally linked to intolerance for delayed rewards, a related form of impulsivity. Methods: We investigated the relationship between D2/3 receptor availability in the NAcb and impulsivity in a delay-discounting task (DDT) where animals must choose between immediate small-magnitude rewards and delayed larger-magnitude rewards...
March 15, 2018: International Journal of Neuropsychopharmacology
Chao Dong, Ji-Chun Zhang, Qian Ren, Min Ma, Youge Qu, Kai Zhang, Wei Yao, Tamaki Ishima, Hisashi Mori, Kenji Hashimoto
The N-methyl-D-aspartate receptor (NMDAR) plays a key role in the pathophysiology of depression. Serine racemase (SRR, encoded by Srr) converts L-serine to D-serine, an endogenous co-agonist at the glycine site of the NMDAR. Knock-out (KO) of Srr did not alter behavioral signs of depression compared with wild-type (WT) mice as evaluated by locomotion, tail suspension, forced swimming, and 1% sucrose preference tests. However, chronic social defeat stress (CSDS: 10 days) caused a depression-like phenotype as measured by these same tests in WT mice but not in Srr KO mice, suggesting that decreased D-serine co-agonist activity confers resilience against CSDS...
March 14, 2018: Neurochemistry International
Zachary S Lorsch, Yong-Hwee Eddie Loh, Immanuel Purushothaman, Deena M Walker, Eric M Parise, Marine Salery, Michael E Cahill, Georgia E Hodes, Madeline L Pfau, Hope Kronman, Peter J Hamilton, Orna Issler, Benoit Labonté, Ann E Symonds, Matthew Zucker, Tie Yuan Zhang, Michael J Meaney, Scott J Russo, Li Shen, Rosemary C Bagot, Eric J Nestler
Most people exposed to stress do not develop depression. Animal models have shown that stress resilience is an active state that requires broad transcriptional adaptations, but how this homeostatic process is regulated remains poorly understood. In this study, we analyze upstream regulators of genes differentially expressed after chronic social defeat stress. We identify estrogen receptor α (ERα) as the top regulator of pro-resilient transcriptional changes in the nucleus accumbens (NAc), a key brain reward region implicated in depression...
March 16, 2018: Nature Communications
Ashley A Yttredahl, Erin McRobert, Benjamin Sheler, Brian J Mickey, Tiffany M Love, Scott A Langenecker, Jon-Kar Zubieta, David T Hsu
INTRODUCTION: Responding adaptively to one's social environment is a key factor predicting the course of major depressive disorder (MDD). Socially rejecting events can exacerbate, whereas socially accepting events can ameliorate depressive symptoms. The neural responses to rejection and acceptance in MDD are relatively unexplored. METHODS: We used functional magnetic resonance imaging (fMRI) to measure neural responses to romantic rejection and acceptance in women diagnosed with current MDD (n = 19) and a matched group of healthy controls (HCs) (n = 19)...
February 27, 2018: Journal of Affective Disorders
Lara M Wierenga, Marieke G N Bos, Elisabeth Schreuders, Ferdi Vd Kamp, Jiska S Peper, Christian K Tamnes, Eveline A Crone
The onset of adolescence in humans is marked by hormonal changes that give rise to secondary sexual characteristics, noted as puberty. It has, however, proven challenging to unravel to what extent pubertal changes may have organizing effects on the brain beyond chronological age, as reported in animal studies. The present longitudinal study aimed to characterize the unique effects of age and puberty on subcortical brain volumes and included three waves of data collection at two-year intervals and 680 T1-weighted MRI scans of 271 participants (54% females) aged between 8 and 29 years old...
March 8, 2018: Psychoneuroendocrinology
J D Santoro, N D Forkert, Q-Z Yang, S Pavitt, S J MacEachern, M E Moseley, K W Yeom
BACKGROUND AND PURPOSE: Tension-type and migraine-type headaches are the most common chronic paroxysmal disorders of childhood. The goal of this study was to compare regional cerebral volumes and diffusion in tension-type and migraine-type headaches against published controls. MATERIALS AND METHODS: Patients evaluated for tension-type or migraine-type headache without aura from May 2014 to July 2016 in a single center were retrospectively reviewed. Thirty-two patients with tension-type headache and 23 with migraine-type headache at an average of 4 months after diagnosis were enrolled...
March 15, 2018: AJNR. American Journal of Neuroradiology
Laura J Mosher, Sean C Godar, Marc Morissette, Kenneth M McFarlin, Simona Scheggi, Carla Gambarana, Stephen C Fowler, Thérèse Di Paolo, Marco Bortolato
The enzyme steroid 5α-reductase 2 (5αR2) catalyzes the conversion of testosterone into the potent androgen 5α-dihydrotestosterone. Previous investigations showed that 5αR2 is expressed in key brain areas for emotional and socio-affective reactivity, yet the role of this enzyme in behavioral regulation remains mostly unknown. Here, we profiled the behavioral characteristics of 5αR2 heterozygous (HZ) and knockout (KO) mice, as compared with their wild-type (WT) littermates. While male 5αR2 KO mice displayed no overt alterations in motoric, sensory, information-processing and anxiety-related behaviors, they exhibited deficits in neurobehavioral correlates of dominance (including aggression against intruders, mating, and tube dominance) as well as novelty-seeking and risk-taking responses...
February 16, 2018: Psychoneuroendocrinology
Lotte F van Dillen, Henk van Steenbergen
The present research examined whether cognitive load modulates the neural processing of appetitive, high-calorie food stimuli. In a functional magnetic resonance imaging (fMRI) study, participants quickly categorized high-calorie and low-calorie food pictures versus object pictures as edible or inedible while they concurrently performed a digit-span task that varied between low and high cognitive load (memorizing six digits vs. one digit). In line with predictions, the digit-span task engaged the dorsolateral prefrontal cortex (DLPFC) when cognitive load was high compared to low...
March 14, 2018: Cognitive, Affective & Behavioral Neuroscience
Eduardo F Gallo, Jozsef Meszaros, Jeremy D Sherman, Muhammad O Chohan, Eric Teboul, Claire S Choi, Holly Moore, Jonathan A Javitch, Christoph Kellendonk
Dopamine D2 receptors (D2Rs) in the nucleus accumbens (NAc) regulate motivated behavior, but the underlying neurobiological mechanisms remain unresolved. Here, we show that selective upregulation of D2Rs in the indirect pathway of the adult NAc enhances the willingness to work for food. Mechanistic studies in brain slices reveal that D2R upregulation attenuates inhibitory transmission at two main output projections of the indirect pathway, the classical long-range projections to the ventral pallidum (VP), as well as local collaterals to direct pathway medium spiny neurons...
March 14, 2018: Nature Communications
Philippe A Melas, Johanna S Qvist, Matteo Deidda, Chirag Upreti, Ya Bin Wei, Fabrizio Sanna, Walter Fratta, Maria Scherma, Paola Fadda, Denise B Kandel, Eric R Kandel
Reduced eukaryotic Initiation Factor 2 (eIF2)α phosphorylation (p-eIF2α) enhances protein synthesis, memory formation, and addiction-like behaviors. However, p-eIF2α has not been examined with regard to psychoactive cannabinoids and cross-sensitization. Here, we find that a cannabinoid receptor agonist (WIN 55,212-2 mesylate [WIN]) reduced p-eIF2α in vitro by upregulating GADD34 (PPP1R15A), the recruiter of protein phosphatase 1 (PP1). The induction of GADD34 was linked to ERK/CREB signaling and to CREB-binding protein (CBP)-mediated histone hyperacetylation at the Gadd34 locus...
March 13, 2018: Cell Reports
Elisabeth Schreuders, Barbara R Braams, Neeltje E Blankenstein, Jiska S Peper, Berna Güroğlu, Eveline A Crone
It was examined how ventral striatum responses to rewards develop across adolescence and early adulthood and how individual differences in state- and trait-level reward sensitivity are related to these changes. Participants (aged 8-29 years) were tested across three waves separated by 2 years (693 functional MRI scans) in an accelerated longitudinal design. The results confirmed an adolescent peak in reward-related ventral striatum, specifically nucleus accumbens, activity. In early to mid-adolescence, increases in reward activation were related to trait-level reward drive...
March 13, 2018: Child Development
Li-Min Mao, Hunter J Faris, John Q Wang
The Src family kinase (SFK) is a subfamily of non-receptor tyrosine kinases. SFK members, Src and especially Fyn, are expressed in the striatum. These SFK members are involved in the regulation of neuronal and synaptic activities and are linked to the pathogenesis of a variety of neuropsychiatric and neurodegenerative disorders. Given the fact that muscarinic acetylcholine (mACh) receptors are highly expressed in striatal neurons and are critical for the regulation of striatal function, we investigated the role of mACh receptors in the regulation of SFKs in the adult rat striatum in vivo...
March 12, 2018: Journal of Molecular Neuroscience: MN
Meaghan Creed
Neuromodulation therapies such as deep brain stimulation or transcranial magnetic stimulation have shown promise in reducing symptoms of addiction when applied to the prefontal cortex, nucleus accumbens or subthalamic nucleus. Pre-clinical investigations implicate modulation of the cortico-basal ganglia network in these therapeutic effects, and this mechanistic understanding is necessary to optimize stimulation paradigms. Recently, the principle that neuromodulation can reverse drug-evoked synaptic plasticity and reduce behavioral symptoms of addiction has inspired novel stimulation paradigms that have long-term effects in animal models...
March 7, 2018: Current Opinion in Neurobiology
Ishan Gupta, Andrew M J Young
The non-competitive glutamate antagonist, phencyclidine is used in rodents to model behavioural deficits see in schizophrenia. Importantly, these deficits endure long after the cessation of short-term chronic treatment (sub-chronic), indicating that the drug treatment causes long-term changes in the physiology and/or chemistry of the brain. There is evidence that this may occur through glutamatergic modulation of mesolimbic dopamine release, perhaps involving metabotropic glutamate receptors (mGluR). This study sought to investigate the effect of sub-chronic phencyclidine pretreatment on modulation of dopamine neurotransmission by metabotropic glutamate receptors 2 and 5 (mGluR2 and mGluR5) in the nucleus accumbens shell in vitro, with the hypothesis that phencyclidine pretreatment would disrupt the mGluR-mediated modulation of dopamine release...
March 7, 2018: Brain Research
Jung Won Lee, Wha Young Kim, Jeong-Hoon Kim
Leptin in the rat's nucleus accumbens (NAcc) core has previously shown to disrupt the effects of acute administration of cocaine on both locomotor activity and the phosphorylation levels of glycogen synthase kinase 3β. In the present study, we further measured the phosphorylation levels of GluA1 after bilateral microinjections of leptin in this site followed by acute administration of cocaine. Interestingly, leptin in the NAcc core significantly blocks the increase of GluA1 phosphorylation levels at serine 845 induced by acute administration of cocaine...
March 8, 2018: Neuroreport
Agnieszka Zagorska, Anna Partyka, Adam Bucki, Alicja Gawalska, Anna Czopek, Maciej Pawlowski
BACKGROUND: The phosphodiesterase 10 (PDE10) family, identified in 1999, is mainly expressed in the brain, particularly in the striatum, within the medium spiny neurons, nucleus accumbens, and olfactory tubercle. Inhibitors of PDE10 (PDE10-Is) are a conceptually rational subject for medicinal chemistry with potential use in the treatment of psychiatric and neurodegenerative diseases. OBJECTIVE: This review is based on peer-reviewed published articles, and summarizes the cellular and molecular biology of PDE10 as a rational target for psychiatric and neurodegenerative drug discovery...
March 8, 2018: Current Medicinal Chemistry
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