scholarly journals A common limiter circuit for opioid choice and relapse identified in a rodent addiction model

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jasper A. Heinsbroek ◽  
Giuseppe Giannotti ◽  
Mitchel R. Mandel ◽  
Megan Josey ◽  
Gary Aston-Jones ◽  
...  
Keyword(s):  
Dendritic Spines ◽  
Food Reinforcement ◽  
Brain Regions ◽  
Infralimbic Cortex ◽  
Nucleus Accumbens Shell ◽  
Food Cues ◽  
Behavioral Constructs ◽  
Relapse Rates ◽  
Subsequent Relapse

AbstractActivity in numerous brain regions drives heroin seeking, but no circuits that limit heroin seeking have been identified. Furthermore, the neural circuits controlling opioid choice are unknown. In this study, we examined the role of the infralimbic cortex (IL) to nucleus accumbens shell (NAshell) pathway during heroin choice and relapse. This model yielded subpopulations of heroin versus food preferring rats during choice, and choice was unrelated to subsequent relapse rates to heroin versus food cues, suggesting that choice and relapse are distinct behavioral constructs. Supporting this, inactivation of the IL with muscimol produced differential effects on opioid choice versus relapse. A pathway-specific chemogenetic approach revealed, however, that the IL-NAshell pathway acts as a common limiter of opioid choice and relapse. Furthermore, dendritic spines in IL-NAshell neurons encode distinct aspects of heroin versus food reinforcement. Thus, opioid choice and relapse share a common addiction-limiting circuit in the IL-NAshell pathway.

scholarly journals Central Role of Cognitive Control Networks in Weight Loss During Voluntary Calorie Restriction

2017 ◽  
Author(s):  
Selin Neseliler ◽  
Wen Hu ◽  
Kevin Larcher ◽  
Maria Zacchia ◽  
Mahsa Dadar ◽  
...  
Keyword(s):  
Weight Loss ◽  
Calorie Restriction ◽  
Cue Reactivity ◽  
Brain Regions ◽  
Self Control ◽  
Food Cues ◽  
Control Networks ◽  
Restriction Diet ◽  
Brain Fmri

SummaryInsufficient responses to hypocaloric diets have been attributed to hormonal adaptations that override self-control of food intake. We tested this hypothesis by measuring brain fMRI reactivity to food cues and circulating energy-balance hormones in 24 overweight/obese participants before, and 1 and 3 months after starting a calorie restriction diet. Increased activity in prefrontal regions at month 1 correlated with weight loss at months 1 and 3. Weight loss was also correlated with increased plasma ghrelin and decreased leptin at month 1, and these changes were associated with greater food cue reactivity in reward-related brain regions. However, the reduction in leptin did not counteract weight loss; indeed, it was correlated with further weight loss at month 3. Activation in a network of prefrontal regions associated with self-control could contribute to individual differences in weight loss and maintenance, whereas we failed to find that the hormonal adaptations play a major role.

scholarly journals Alterations in Rat Accumbens Dopamine, Endocannabinoids and GABA Content During WIN55,212-2 Treatment: The Role of Ghrelin

2020 ◽  
Vol 22 (1) ◽  
pp. 210
Author(s):  
Chrysostomos Charalambous ◽  
Marek Lapka ◽  
Tereza Havlickova ◽  
Kamila Syslova ◽  
Magdalena Sustkova-Fiserova
Keyword(s):  
Nucleus Accumbens ◽  
Food Intake ◽  
Dopamine Release ◽  
Brain Regions ◽  
Aminobutyric Acid ◽  
Gamma Aminobutyric Acid ◽  
Nucleus Accumbens Shell ◽  
Gaba Content ◽  
Dopamine Efflux

The endocannabinoid/CB1R system as well as the central ghrelin signalling with its growth hormone secretagogoue receptors (GHS-R1A) are importantly involved in food intake and reward/reinforcement processing and show distinct overlaps in distribution within the relevant brain regions including the hypothalamus (food intake), the ventral tegmental area (VTA) and the nucleus accumbens (NAC) (reward/reinforcement). The significant mutual interaction between these systems in food intake has been documented; however, the possible role of ghrelin/GHS-R1A in the cannabinoid reinforcement effects and addiction remain unclear. Therefore, the principal aim of the present study was to investigate whether pretreatment with GHS-R1A antagonist/JMV2959 could reduce the CB1R agonist/WIN55,212-2–induced dopamine efflux in the nucleus accumbens shell (NACSh), which is considered a crucial trigger impulse of the addiction process. The synthetic aminoalklylindol cannabinoid WIN55,212-2 administration into the posterior VTA induced significant accumbens dopamine release, which was significantly reduced by the 3 mg/kg i.p. JMV2959 pretreatment. Simultaneously, the cannabinoid-increased accumbens dopamine metabolic turnover was significantly augmented by the JMV2959 pretreament. The intracerebral WIN55,212-2 administration also increased the endocannabinoid arachidonoylethanolamide/anandamide and the 2-arachidonoylglycerol/2-AG extracellular levels in the NACSh, which was moderately but significantly attenuated by the JMV2959 pretreatment. Moreover, the cannabinoid-induced decrease in accumbens γ-aminobutyric acid/gamma-aminobutyric acid levels was reversed by the JMV2959 pretreatment. The behavioural study in the LABORAS cage showed that 3 mg/kg JMV2959 pretreatment also significantly reduced the systemic WIN55,212-2-induced behavioural stimulation. Our results demonstrate that the ghrelin/GHS-R1A system significantly participates in the rewarding/reinforcing effects of the cannabinoid/CB1 agonist that are involved in cannabinoid addiction processing.

Synaptic organization of the gustatory NST

1994 ◽  
Vol 52 ◽  
pp. 150-151
Author(s):  
M. C. Whitehead
Keyword(s):  
Central Nervous System ◽  
Dendritic Spines ◽  
Fundamental Problem ◽  
Cell Types ◽  
Brain Regions ◽  
Excitatory Synapses ◽  
Solitary Tract ◽  
Synaptic Organization ◽  
Synaptic Junctions ◽  
Afferent Terminals

A fundamental problem in taste research is to determine how gustatory signals are processed and disseminated in the mammalian central nervous system. An important first step toward understanding information processing is the identification of cell types in the nucleus of the solitary tract (NST) and their synaptic relationships with oral primary afferent terminals. Facial and glossopharyngeal (LIX) terminals in the hamster were labelled with HRP, examined with EM, and characterized as containing moderate concentrations of medium-sized round vesicles, and engaging in asymmetrical synaptic junctions. Ultrastructurally the endings resemble excitatory synapses in other brain regions.Labelled facial afferent endings in the RC subdivision synapse almost exclusively with distal dendrites and dendritic spines of NST cells. Most synaptic relationships between the facial synapses and the dendrites are simple. However, 40% of facial endings engage in complex synaptic relationships within glomeruli containing unlabelled axon endings particularly ones termed "SP" endings. SP endings are densely packed with small, pleomorphic vesicles and synapse with both the facial endings and their postsynaptic dendrites by means of nearly symmetrical junctions.

scholarly journals Does intervention with GLP-1 receptor agonist semaglutide modulate perception of sweet taste in women with obesity: study protocol of a randomized, single-blinded, placebo-controlled clinical trial

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Mojca Jensterle ◽  
Simona Ferjan ◽  
Tadej Battelino ◽  
Jernej Kovač ◽  
Saba Battelino ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Neural Response ◽  
Taste Perception ◽  
Taste Bud ◽  
Controlled Clinical Trial ◽  
Food Cues ◽  
Link Type ◽  
Visual Food Cues ◽  
Taste Bud Cells

Abstract Background Preclinical studies demonstrated that glucagon-like peptide 1 (GLP-1) is locally synthesized in taste bud cells and that GLP-1 receptor exists on the gustatory nerves in close proximity to GLP-1-containing taste bud cells. This local paracrine GLP-1 signalling seems to be specifically involved in the perception of sweets. However, the role of GLP-1 in taste perception remains largely unaddressed in clinical studies. Whether any weight-reducing effects of GLP-1 receptor agonists are mediated through the modulation of taste perception is currently unknown. Methods and analysis This is an investigator-initiated, randomized single-blind, placebo-controlled clinical trial. We will enrol 30 women with obesity and polycystic ovary syndrome (PCOS). Participants will be randomized in a 1:1 ratio to either semaglutide 1.0 mg or placebo for 16 weeks. The primary endpoints are alteration of transcriptomic profile of tongue tissue as changes in expression level from baseline to follow-up after 16 weeks of treatment, measured by RNA sequencing, and change in taste sensitivity as detected by chemical gustometry. Secondary endpoints include change in neural response to visual food cues and to sweet-tasting substances as assessed by functional MRI, change in body weight, change in fat mass and change in eating behaviour and food intake. Discussion This is the first study to investigate the role of semaglutide on taste perception, along with a neural response to visual food cues in reward processing regions. The study may identify the tongue and the taste perception as a novel target for GLP-1 receptor agonists. Ethics and disseminations The study has been approved by the Slovene National Medical Ethics Committee and will be conducted in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines. Results will be submitted for publication in an international peer-reviewed scientific journal. Trial registration ClinicalTrials.govNCT04263415. Retrospectively registered on 10 February 2020

scholarly journals The G Protein-Coupled Glutamate Receptors as Novel Molecular Targets in Schizophrenia Treatment—A Narrative Review

2021 ◽  
Vol 10 (7) ◽  
pp. 1475
Author(s):  
Waldemar Kryszkowski ◽  
Tomasz Boczek
Keyword(s):  
Glutamate Receptors ◽  
Metabotropic Glutamate Receptors ◽  
Glutamate Release ◽  
Molecular Targets ◽  
Brain Regions ◽  
Psychotic Symptoms ◽  
Unknown Etiology ◽  
Metabotropic Glutamate ◽  
G Protein Coupled

Schizophrenia is a severe neuropsychiatric disease with an unknown etiology. The research into the neurobiology of this disease led to several models aimed at explaining the link between perturbations in brain function and the manifestation of psychotic symptoms. The glutamatergic hypothesis postulates that disrupted glutamate neurotransmission may mediate cognitive and psychosocial impairments by affecting the connections between the cortex and the thalamus. In this regard, the greatest attention has been given to ionotropic NMDA receptor hypofunction. However, converging data indicates metabotropic glutamate receptors as crucial for cognitive and psychomotor function. The distribution of these receptors in the brain regions related to schizophrenia and their regulatory role in glutamate release make them promising molecular targets for novel antipsychotics. This article reviews the progress in the research on the role of metabotropic glutamate receptors in schizophrenia etiopathology.

scholarly journals Development-Dependent Plasticity in Vasoactive Intestinal Polypeptide Neurons in the Infralimbic Cortex

2021 ◽  
Vol 2 (1) ◽  
Author(s):  
Stuart A Collins ◽  
Ipe Ninan
Keyword(s):  
Sex Differences ◽  
Anxiety Disorders ◽  
Vasoactive Intestinal Polypeptide ◽  
Cortical Plasticity ◽  
Male Mice ◽  
Infralimbic Cortex ◽  
Membrane Excitability ◽  
Gabaergic Transmission ◽  
Intestinal Polypeptide

Abstract The onset of several neuropsychiatric disorders including anxiety disorders coincides with adolescence. Consistently, threat extinction, which plays a key role in the regulation of anxiety-related behaviors, is diminished during adolescence. Furthermore, this attenuated threat extinction during adolescence is associated with an altered synaptic plasticity in the infralimbic medial prefrontal cortex (IL-mPFC), a brain region critical for threat extinction. However, the mechanism underlying the altered plasticity in the IL-mPFC during adolescence is unclear. Given the purported role of vasoactive intestinal polypeptide expressing interneurons (VIPINs) in disinhibition and hence their potential to affect cortical plasticity, we examined whether VIPINs exhibit an adolescence-specific plasticity in the IL-mPFC. We observed an increase in GABAergic transmission and a decrease in excitability in VIPINs during adolescence. Male mice show a significantly higher VIPIN-pyramidal neuron GABAergic transmission compared with female mice. The observed increase in GABAergic transmission and a decrease in membrane excitability in VIPINs during adolescence could play a role in the altered plasticity in the adolescent IL-mPFC. Furthermore, the suppression of VIPIN-mediated GABAergic transmission in females might be relevant to sex differences in anxiety disorders.

scholarly journals The Protective Role of Brain CYP2J in Parkinson’s Disease Models

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Yueran Li ◽  
Jinhua Wu ◽  
Xuming Yu ◽  
Shufang Na ◽  
Ke Li ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Brain Regions ◽  
Protective Role ◽  
Neural Cells ◽  
Endogenous Substrates ◽  
6 Hydroxydopamine ◽  
Myd88 Signaling ◽  
Lps Treatment

CYP2J proteins are present in the neural cells of human and rodent brain regions. The aim of this study was to investigate the role of brain CYP2J in Parkinson’s disease. Rats received right unilateral injection with lipopolysaccharide (LPS) or 6-hydroxydopamine (6-OHDA) in the substantia nigra following transfection with or without the CYP2J3 expression vector. Compared with LPS-treated rats, CYP2J3 transfection significantly decreased apomorphine-induced rotation by 57.3% at day 12 and 47.0% at day 21 after LPS treatment; moreover, CYP2J3 transfection attenuated the accumulation of α-synuclein. Compared with the 6-OHDA group, the number of rotations by rats transfected with CYP2J3 decreased by 59.6% at day 12 and 43.5% at day 21 after 6-OHDA treatment. The loss of dopaminergic neurons and the inhibition of the antioxidative system induced by LPS or 6-OHDA were attenuated following CYP2J3 transfection. The TLR4-MyD88 signaling pathway was involved in the downregulation of brain CYP2J induced by LPS, and CYP2J transfection upregulated the expression of Nrf2 via the inhibition of miR-340 in U251 cells. The data suggest that increased levels of CYP2J in the brain can delay the pathological progression of PD initiated by inflammation or neurotoxins. The alteration of the metabolism of the endogenous substrates (e.g., AA) could affect the risk of neurodegenerative disease.

Electroencephalographic Recordings of Focal Seizures in Patients Affected by Periventricular Nodular Heterotopia: Role of the Heterotopic Nodules in the Genesis of Epileptic Discharges

2004 ◽  
Vol 19 (3) ◽  
pp. 369-377
Author(s):  
Giorgio Battaglia ◽  
Silvana Franceschetti ◽  
Luisa Chiapparini ◽  
Elena Freri ◽  
Stefania Bassanini ◽  
...  
Keyword(s):  
Brain Regions ◽  
Periventricular Nodular Heterotopia ◽  
Focal Seizures ◽  
Ictal Eeg ◽  
Epileptic Discharges ◽  
Nodular Heterotopia ◽  
Eeg Recordings ◽  
Drug Resistant Epilepsy ◽  
Video Eeg

Patients affected by periventricular nodular heterotopia are frequently characterized by focal drug-resistant epilepsy. To investigate the role of periventricular nodules in the genesis of seizures, we analyzed the electroencephalographic (EEG) features of focal seizures recorded by means of video-EEG in 10 patients affected by different types of periventricular nodular heterotopia and followed for prolonged periods of time at the epilepsy center of our institute. The ictal EEG recordings with surface electrodes revealed common features in all patients: all seizures originated from the brain regions where the periventricular nodular heterotopia were located; EEG patterns recorded on the leads exploring the periventricular nodular heterotopia were very similar both at the onset and immediately after the seizure's end in all patients. Our data suggest that seizures are generated by abnormal anatomic circuitries, including the heterotopic nodules and adjacent cortical areas. The major role of heterotopic neurons in the genesis and propagation of epileptic discharges must be taken into account when planning surgery for epilepsy in patients with periventricular nodular heterotopia. ( J Child Neurol 2005;20:369—377).

scholarly journals Activity in the brain’s valuation and mentalizing networks is associated with propagation of online recommendations

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Elisa C. Baek ◽  
Matthew Brook O’Donnell ◽  
Christin Scholz ◽  
Rui Pei ◽  
Javier O. Garcia ◽  
...  
Keyword(s):  
Social Media ◽  
Word Of Mouth ◽  
Mental States ◽  
Brain Regions ◽  
Prior Work ◽  
Opinion Change ◽  
Wide Range ◽  
The Mind ◽  
Mentalizing System

AbstractWord of mouth recommendations influence a wide range of choices and behaviors. What takes place in the mind of recommendation receivers that determines whether they will be successfully influenced? Prior work suggests that brain systems implicated in assessing the value of stimuli (i.e., subjective valuation) and understanding others’ mental states (i.e., mentalizing) play key roles. The current study used neuroimaging and natural language classifiers to extend these findings in a naturalistic context and tested the extent to which the two systems work together or independently in responding to social influence. First, we show that in response to text-based social media recommendations, activity in both the brain’s valuation system and mentalizing system was associated with greater likelihood of opinion change. Second, participants were more likely to update their opinions in response to negative, compared to positive, recommendations, with activity in the mentalizing system scaling with the negativity of the recommendations. Third, decreased functional connectivity between valuation and mentalizing systems was associated with opinion change. Results highlight the role of brain regions involved in mentalizing and positive valuation in recommendation propagation, and further show that mentalizing may be particularly key in processing negative recommendations, whereas the valuation system is relevant in evaluating both positive and negative recommendations.

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