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ventral tegmental area (VTA)

René Garduño-Gutiérrez, Martha León-Olea, Gabriela Rodríguez-Manzo
Sexual experience modifies brain functioning and copulatory efficiency. Sexual activity, ejaculation in particular, is a rewarding behavior associated with the release of endogenous opioids, which modulate the activity of the mesolimbic dopaminergic system (MLS). In sexually exhausted rats, repeated ejaculation produces μ (MOR) and δ opioid receptor (DOR) internalization in ventral tegmental area (VTA) neurons, as well as long-lasting behavioral changes suggestive of brain plasticity processes. We hypothesized that in sexually naïve rats the endogenous opioids released during sexual experience acquisition, might contribute to brain plasticity processes involved in the generation of the behavioral changes induced by sexual experience...
March 18, 2018: Physiology & Behavior
Ashley C Nelson, Stephanie B Williams, Stephanie S Pistorius, Hyun J Park, Taylor J Woodward, Andrew J Payne, J Daniel Obray, Samuel I Shin, Jennifer K Mabey, Scott C Steffensen
The neural mechanisms underlying alcohol dependence are not well-understood. GABAergic neurons in the ventral tegmental area (VTA) are a relevant target for ethanol. They are inhibited by ethanol at physiologically-relevant levels in vivo and display marked hyperexcitability during withdrawal. In the present study, we examined the effects of the GABA(A) receptor agonist muscimol on VTA neurons ex vivo following withdrawal from acute and chronic ethanol exposure. We used standard cell-attached mode electrophysiology in the slice preparation to evaluate the effects of muscimol on VTA GABA neuron firing rate following exposure to acute and chronic ethanol in male CD-1 GAD-67 GFP mice...
2018: Frontiers in Neuroscience
Sina Faton, Jean-Pol Tassin, Flore Duranton, Didier Bagnol, Anne-Dominique Lajoix
Central serotonin systems have long been associated with the control of feeding behavior and the modulation of behavioral effects of psychostimulants. 5-HT2C receptors are present in hypothalamic centers such as the arcuate nucleus (ARC), controlling homeostatic regulation of food intake, as well as in the ventral tegmental area (VTA), a region involved in motivation aspects in multiple behaviors, including feeding. In the present study, we investigated whether the 5-HT2C receptors control amphetamine-evoked locomotor activity and regulate food consumption...
March 16, 2018: Behavioural Brain Research
Chang You, Bertha Vandegrift, Mark S Brodie
The ventral tegmental area (VTA) evaluates salience of environmental stimuli and provides dopaminergic innervation to many brain areas affected by acute and chronic ethanol exposure. While primarily associated with rewarding and reinforcing stimuli, recent evidence indicates a role for the VTA in aversion as well. Ethanol actions in the VTA may trigger neuroadaptation resulting in reduction of the aversive responses to alcohol and a relative increase in the rewarding responses. In searching for effective pharmacotherapies for the treatment of alcohol abuse and alcoholism, recognition of this imbalance may reveal novel strategies...
March 16, 2018: Psychopharmacology
Poornima Kumar, Franziska Goer, Laura Murray, Daniel G Dillon, Miranda L Beltzer, Andrew L Cohen, Nancy H Brooks, Diego A Pizzagalli
Anhedonia (hyposensitivity to rewards) and negative bias (hypersensitivity to punishments) are core features of major depressive disorder (MDD), which could stem from abnormal reinforcement learning. Emerging evidence highlights blunted reward learning and reward prediction error (RPE) signaling in the striatum in MDD, although inconsistencies exist. Preclinical studies have clarified that ventral tegmental area (VTA) neurons encode RPE and habenular neurons encode punishment prediction error (PPE), which are then transmitted to the striatum and cortex to guide goal-directed behavior...
February 26, 2018: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Luqing Wei, Xiao Hu, Yonggui Yuan, Weiguo Liu, Hong Chen
Neuropathology suggests that Parkinson's disease (PD) with depression may involve a progressive degeneration of the nigrostriatal and mesocorticolimbic dopaminergic systems. Previous positron emission tomography (PET) and single-photon emission computed tomography (SPECT) studies have shown that dopamine changes in individual brain regions constituting the nigrostriatal and mesocorticolimbic circuits are associated with depression in PD. However, few studies have been conducted on the circuit-level alterations in this disease...
March 9, 2018: Behavioural Brain Research
Jorge Tovar-Díaz, Matthew B Pomrenze, Russell Kan, Bahram Pahlavan, Hitoshi Morikawa
Stressful events rapidly trigger activity-dependent synaptic plasticity, driving the formation of aversive memories. However, it remains unclear how stressful experience affects plasticity mechanisms to regulate appetitive learning, such as intake of addictive drugs. Using rats, we show that corticotropin-releasing factor (CRF) and α1 adrenergic receptor (α1AR) signaling enhance the plasticity of NMDA-receptor-mediated glutamatergic transmission in ventral tegmental area (VTA) dopamine (DA) neurons through distinct effects on inositol 1,4,5-triphosphate (IP3 )-dependent Ca2+ signaling...
March 6, 2018: Cell Reports
Michael J Minzenberg, Jong H Yoon, Steffan K Soosman, Cameron S Carter
Candidate pro-cognitive drugs for schizophrenia targeting several neurochemical systems have consistently failed to demonstrate robust efficacy. It remains untested whether concurrent antipsychotic medications exert pharmacodynamic interactions that mitigate pro-cognitive action in patients. We used functional MRI (fMRI) in a randomized, double-blind, placebo-controlled within-subject crossover test of single-dose modafinil effects in 27 medicated schizophrenia patients, interrogating brainstem regions where catecholamine systems arise to innervate the cortex, to link cellular and systems-level models of cognitive control...
March 6, 2018: Translational Psychiatry
Xian Wang, Shaolei Ma, Haibo Wu, Xiaofeng Shen, Shiqin Xu, Xirong Guo, Maria L Bolick, Shizheng Wu, Fuzhou Wang
Our previous works disclosed the contributing role of macrophage migration inhibitory factor (MIF) and dopaminergic inhibition by lysine dimethyltransferase G9a/Glp complex in peripheral nerve injury-induced hypersensitivity. We herein propose that the proinflammatory cytokine MIF participates in the regulation of neuropathic hypersensitivity by interacting with and suppressing the descending dopaminergic system. The lumbar spinal cord (L-SC) and ventral tegmental area (VTA) are two major locations with significant upregulation of MIF after chronic constriction injury (CCI) of the sciatic nerve, and they display time-dependent changes, along with a behavioral trajectory...
February 16, 2018: Experimental & Molecular Medicine
Nicole S Hernandez, Kelsey Y Ige, Elizabeth G Mietlicki-Baase, Gian Carlo Molina-Castro, Christopher A Turner, Matthew R Hayes, Heath D Schmidt
Novel molecular targets are needed to develop new medications for the treatment of cocaine addiction. Here we investigated a role for glucagon-like peptide-1 (GLP-1) receptors in the reinstatement of cocaine-seeking behavior, an animal model of relapse. We showed that peripheral administration of the GLP-1 receptor agonist exendin-4 dose dependently reduced cocaine seeking in rats at doses that did not affect ad libitum food intake, meal patterns or body weight. We also demonstrated that systemic exendin-4 penetrated the brain where it putatively bound receptors on both neurons and astrocytes in the ventral tegmental area (VTA)...
February 14, 2018: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Vivek R Athalye, Fernando J Santos, Jose M Carmena, Rui M Costa
Thorndike's law of effect states that actions that lead to reinforcements tend to be repeated more often. Accordingly, neural activity patterns leading to reinforcement are also reentered more frequently. Reinforcement relies on dopaminergic activity in the ventral tegmental area (VTA), and animals shape their behavior to receive dopaminergic stimulation. Seeking evidence for a neural law of effect, we found that mice learn to reenter more frequently motor cortical activity patterns that trigger optogenetic VTA self-stimulation...
March 2, 2018: Science
Lauren Faget, Vivien Zell, Elizabeth Souter, Adam McPherson, Reed Ressler, Navarre Gutierrez-Reed, Ji Hoon Yoo, Davide Dulcis, Thomas S Hnasko
The ventral pallidum (VP) lies at the interface between sensory, motor, and cognitive processing-with a particular role in mounting behavioral responses to rewards. Though the VP is predominantly GABAergic, glutamate neurons were recently identified, though their relative abundances and respective roles are unknown. Here, we show that VP glutamate neurons are concentrated in the rostral ventromedial VP and project to qualitatively similar targets as do VP GABA neurons. At the functional level, we used optogenetics to show that activity in VP GABA neurons can drive positive reinforcement, particularly through projections to the ventral tegmental area (VTA)...
February 27, 2018: Nature Communications
Erin Hisey, Matthew Gene Kearney, Richard Mooney
The complex skills underlying verbal and musical expression can be learned without external punishment or reward, indicating their learning is internally guided. The neural mechanisms that mediate internally guided learning are poorly understood, but a circuit comprising dopamine-releasing neurons in the midbrain ventral tegmental area (VTA) and their targets in the basal ganglia are important to externally reinforced learning. Juvenile zebra finches copy a tutor song in a process that is internally guided and, in adulthood, can learn to modify the fundamental frequency (pitch) of a target syllable in response to external reinforcement with white noise...
February 26, 2018: Nature Neuroscience
Abigail M Polter, Kelsey Barcomb, Ayumi C Tsuda, Julie A Kauer
Ventral tegmental area (VTA) dopaminergic neurons are key components of the reward pathway, and their activity is powerfully controlled by a diverse array of inhibitory GABAergic inputs. Two major sources of GABAergic nerve terminals within the VTA are local VTA interneurons and neurons in the rostromedial tegmental nucleus (RMTg). Here, using optogenetics, we compared synaptic properties of GABAergic synapses on VTA dopamine neurons using selective activation of afferents that originate from these two cell populations...
February 26, 2018: European Journal of Neuroscience
Fumiya Shinohara, Yuta Asaoka, Hironori Kamii, Masabumi Minami, Katsuyuki Kaneda
Effects of stress on the reward system are well established in the literature. Although previous studies have revealed that stress can reinstate extinguished addictive behaviors related to cocaine, the effects of stress on the rewarding memory of cocaine are not fully understood. Here, we provide evidence that stress potentiates the expression of rewarding memory of cocaine via the activation of brainstem-reward circuitry using a cocaine-induced conditioned place preference (CPP) paradigm combined with restraint stress in rats...
February 26, 2018: Addiction Biology
Hillary L Woodworth, Juliette A Brown, Hannah M Batchelor, Raluca Bugescu, Gina M Leinninger
Pharmacologic treatment with the neuropeptide neurotensin (Nts) modifies motivated behaviors such as feeding, locomotor activity, and reproduction. Dopamine (DA) neurons of the ventral tegmental area (VTA) control these behaviors, and Nts directly modulates the activity of DA neurons via Nts receptor-1. While Nts sources to the VTA have been described in starlings and rats, the endogenous sources of Nts to the VTA of mice remain incompletely understood, impeding determination of which Nts circuits orchestrate specific behaviors in this model...
February 15, 2018: Neuropeptides
Song Zhang, Hongxing Zhang, Stacy M Ku, Barbara Juarez, Carole Morel, Nikos Tzavaras, Sarah Montgomery, Georgia E Hodes, Anna Brancato, Scott J Russo, Jun-Li Cao, Ming-Hu Han
Women are twice as likely to be diagnosed with major depressive disorder. However, fewer studies in rodent models of depression have used female animals, leading to a relative lack of understanding of the female brain's response to stress, especially at a neural circuit level. In this study, we utilized a 6-day subchronic variable stress (SCVS) mouse model and measured novelty suppressed feeding as behavioral criteria to evaluate susceptibility to SCVS in male and female mice. First, we showed that SCVS induced a decrease in latency to eat (susceptible phenotype) in female mice, but not in males (resilient phenotype)...
February 22, 2018: Neuroscience
Jeroen P H Verharen, Johannes W de Jong, Theresia J M Roelofs, Christiaan F M Huffels, Ruud van Zessen, Mieneke C M Luijendijk, Ralph Hamelink, Ingo Willuhn, Hanneke E M den Ouden, Geoffrey van der Plasse, Roger A H Adan, Louk J M J Vanderschuren
Hyperdopaminergic states in mental disorders are associated with disruptive deficits in decision making. However, the precise contribution of topographically distinct mesencephalic dopamine pathways to decision-making processes remains elusive. Here we show, using a multidisciplinary approach, how hyperactivity of ascending projections from the ventral tegmental area (VTA) contributes to impaired flexible decision making in rats. Activation of the VTA-nucleus accumbens pathway leads to insensitivity to loss and punishment due to impaired processing of negative reward prediction errors...
February 21, 2018: Nature Communications
Moon Yi Ko, Eun Young Jang, June Yeon Lee, Su Phil Kim, Sung Hun Whang, Bong Hyo Lee, Hee Young Kim, Char Ha Yang, Hee Jung Cho, Young Seob Gwak
Spinal cord injury (SCI) frequently results in chronic neuropathic pain (CNP). However, the understanding of brain neural circuits in CNP modulation is unclear. The present study examined the changes of ventral tegmental area (VTA) putative GABAergic and dopaminergic neuronal activity with CNP attenuation in rats. SCI was established by T10 clip compression injury (35 g, 1 min) in rats, and neuropathic pain behaviors, in vivo extracellular single cell recording of putative VTA GABA/dopamine neurons, extracellular GABA level, glutamic acid decarboxylase (GAD) and vesicular GABA transporters (VGAT) were measured in the VTA, respectively...
February 21, 2018: Journal of Neurotrauma
Hillary L Woodworth, Patricia A Perez-Bonilla, Bethany G Beekly, Trevor J Lewis, Gina M Leinninger
Neurotensin (Nts) promotes activation of dopamine (DA) neurons in the ventral tegmental area (VTA) via incompletely understood mechanisms. Nts can signal via the G protein-coupled Nts receptors 1 and 2 (NtsR1 and NtsR2), but the lack of methods to detect NtsR1- and NtsR2-expressing cells has limited mechanistic understanding of Nts action. To overcome this challenge, we generated dual recombinase mice that express FlpO-dependent Cre recombinase in NtsR1 or NtsR2 cells. This strategy permitted temporal control over recombination, such that we could identify NtsR1- or NtsR2-expressing cells and determine whether their distributions differed between the developing and adult brain...
January 2018: ENeuro
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