Mesolimbic Research Articles

Intra-accumbal orexinergic system contributes to the stress-induced antinociceptive behaviors in the animal model of acute pain in rats.

Stress and pain are interleaved at numerous levels - influencing each other. Stress can increase the nociception threshold in animals, long-known as stress-induced analgesia (SIA). Orexin is known as a neuropeptide that modulates pain. The effect of stress on the mesolimbic system in the modulation of pain is known. The role of the intra-accumbal orexin receptors in the modulation of acute pain by forced swim stress (FSS) is unclear. In this study, 117 adult male albino Wistar rats (270-300 g) were used. The animals were unilaterally implanted with cannulae above the NAc. The antagonist of the orexin-1 receptor (OX1r), SB334867, and antagonist of the orexin-2 receptor (OX2r), TCS OX2 29, were microinjected into the NAc in different doses (1, 3, 10, and 30 nmol/0.5 µl DMSO) before exposure to FSS for a 6-min period. The tail-flick test was carried out as an assay nociception of acute pain, and the nociceptive threshold [tail-flick latency (TFL)] was measured for 60-minute. The findings demonstrated that exposure to acute stress could remarkably increase the TFLs and antinociceptive responses. Moreover, intra-accumbal microinjection of SB334867 or TCS OX2 29 blocked the antinociceptive effect of stress in the tail-flick test. The contribution of orexin receptors was almost equally modulating SIA. The present study's findings suggest that OX1r and OX2r within the NAc modulate stress-induced antinociceptive responses. The intra-accumbal microinjection of orexin receptors antagonists declares inducing antinociceptive responses by FSS in acute pain. Proposedly, intra-accumbla orexinergic receptors have a role in the development of SIA.

“Correlation does not Imply Causation”, while Psychotropic Drugs do cause Neurochemical Imbalances and Dysfunction of Neurotransmission

Mental health professionals often prescribe psychotropic drugs to patients diagnosed with mental health illnesses under the premise that neurochemical imbalance is a main underlying cause of mental health disorders. In this paper we discuss reasons to believe that there is no scientific research which provides evidence that neurochemical imbalances or problems with neurotransmission in the brain are causative factors in the etiology of mental health illnesses. Behavioral and neurochemical research studies in animals show an ASSOCIATION between mental health states and alteration of neurotransmitter signaling. However, correlation does not imply causation. To the contrary, stress paradigms in rodents show a diminishing of the activity of the mesolimbic dopaminergic reward pathway _as a result of_ long-term stressful stimuli. Furthermore, studies in human cases of mental health disorders show that psychotropic drugs cause disturbances in neurotransmission or neurochemical homeostasis as seen in biochemical research studies, and this is manifest by the behavioral consequences experienced during withdrawal in humans and animals. SIGNIFICANCE: This paper presents reasons to question the safety and efficacy of the common use of psychotropic drugs in the mental health industry.

Lower Dorsal Putamen D2/3 Receptor Availability and Amphetamine-Induced Dopamine Release are Related to Poorer Cognitive Function in Recently Abstinent People Who Smoke and Healthy Controls.

In the dopamine system, the mesolimbic pathway, including the dorsal striatum, underlies the reinforcing properties of tobacco smoking, and the mesocortical pathway, including the dorsolateral prefrontal cortex (dlPFC), is critical for cognitive functioning. Dysregulated dopamine signaling has been linked to drug-seeking behaviors and cognitive deficits. The dorsal striatum and dlPFC are structurally and functionally connected and are key regions for cognitive functioning. We recently showed that people who smoke have lower dlPFC dopamine (D2/3R) receptor availability than people who do not, which is related to poorer cognitive function. The goal of this study was to examine the same brain-behavior relationship in the dorsal striatum. Twenty-nine (18 males) recently abstinent people who smoke and 29 sex-matched healthy controls participated in 2 same-day [11C]-(+)-PHNO positron emission tomography scans before and after amphetamine administration to provoke dopamine release. D2/3R availability (binding potential; BPND) and amphetamine-induced dopamine release (%ΔBPND) were calculated. Cognition (verbal learning and memory) was assessed with the CogState computerized battery. There were no group differences in baseline BPND. People who smoke have a smaller magnitude %ΔBPND in dorsal putamen than healthy controls (p = .022). People who smoke perform worse on immediate (p = .035) and delayed (p = .011) recall than healthy controls. In all people, lower dorsal putamen BPND was associated with worse immediate (p = .006) and delayed recall (p = .049), and lower %ΔBPND was related to worse delayed recall (p = .022). Lower dorsal putamen D2/3R availability and function are associated with disruptions in cognitive function that may underlie difficulty with resisting smoking. This study directly relates dopamine imaging outcomes in the dorsal striatum to cognitive function in recently abstinent people who smoke cigarettes and healthy controls. The current work included a well-characterized subject sample in terms of demographics, smoking characteristics, and a validated neurocognitive test of verbal learning and memory. The findings of this study extend previous literature relating dopamine imaging outcomes to cognition in recently abstinent people who smoke and people who do not smoke, expanding our understanding of brain-behavior relationships.

NAc-DBS corrects depression-like behaviors in CUMS mouse model via disinhibition of DA neurons in the VTA.

Major depressive disorder (MDD) is characterized by diverse debilitating symptoms that include loss of motivation and anhedonia. If multiple medications, psychotherapy, and electroconvulsive therapy fail in some patients with MDD, their condition is then termed treatment-resistant depression (TRD). MDD can be associated with abnormalities in the reward-system-dopaminergic mesolimbic pathway, in which the nucleus accumbens (NAc) and ventral tegmental area (VTA) play major roles. Deep brain stimulation (DBS) applied to the NAc alleviates the depressive symptoms of MDD. However, the mechanism underlying the effects of this DBS has remained elusive. In this study, using the chronic unpredictable mild stress (CUMS) mouse model, we investigated the behavioral and neurobiological effects of NAc-DBS on the multidimensional depression-like phenotypes induced by CUMS by integrating behavioral, in vivo microdialysis coupled with high-performance liquid chromatography-electrochemical detector (HPLC-ECD), calcium imaging, pharmacological, and genetic manipulation methods in freely moving mice. We found that long-term and repeated, but not single, NAc-DBS induced robust antidepressant responses in CUMS mice. Moreover, even a single trial NAc-DBS led to the elevation of the γ-aminobutyric acid (GABA) neurotransmitter, accompanied by the increase in dopamine (DA) neuron activity in the VTA. Both the inhibition of the GABAA receptor activity and knockdown of the GABAA-α1 gene in VTA-GABA neurons blocked the antidepressant effect of NAc-DBS in CUMS mice. Our results showed that NAc-DBS could disinhibit VTA-DA neurons by regulating the level of GABA and the activity of VTA-GABA in the VTA and could finally correct the depression-like behaviors in the CUMS mouse model.

Selective orexin 1 receptor antagonism does not affect effort-based responding for sucrose reward in rats.

In rodents, orexin neuropeptides regulate motivation and reward-seeking via orexin 1 receptor (OX1R) signaling in the mesolimbic dopaminergic system. This role is clearly established for rewards inherent to drugs of abuse but less so for natural rewards. Reported effects of the selective OX1R antagonist (SO1RA) SB-334867 on motivation for palatable food are ambiguous. In our experimental conditions neither SB-334867, nor two additional, structurally different SO1RAs, ACT-335827 and the clinical development candidate nivasorexant, affected effort-based responding for sucrose in rats. The positive control lisdexamfetamine, approved for psychiatric disorders associated with altered reward sensitivity such as binge eating disorder, increased effort-based responding.

Short-term effects of semaglutide among patients with obesity with and without food addiction: an observational study

Introduction Food addiction (FA) is highly prevalent among people with obesity (PwO) and may constitute a key factor in weight loss failure or weight regain. GLP-1 analogues have been shown to act on the mesolimbic system, which is related to hedonic overeating and substance abuse. We aimed to study the effects of low doses of semaglutide on FA symptomatology and to evaluate whether the presence of FA have a negative impact on weight loss despite treatment with semaglutide. Methods One hundred and thirteen PwO (45.5 ± 10.2 years) were evaluated anthropometrically baseline and after four months of treatment with semaglutide. PwO were evaluated for the presence of FA by completing The Spanish version of the Yale Food Addiction Scale 2.0 questionnaire (YFAS 2.0). Results Baseline BMI and fat mass (%) were greater among PwO with FA (35.8 ± 4.5 vs 33 ± 3.9 kg/m2and 44.2 ± 6.5 vs 40.1 ± 7.9%; p = .01). After four months of treatment with semaglutide, the prevalence of FA diminished from 57.5% to 4.2% (p < .001). The percentage of weight loss (6.9 ± 12.7 vs 5.3 ± 4.6%; p = .4) and the proportion of fat mass loss (2 ± 9 vs 1.6 ± 3.1%; p = .7) were comparable between PwO with and without FA. No differences regarding side effects and treatment discontinuations were seen between the two groups Conclusion Semaglutide is an effective tool for the amelioration of FA symptomatology among PwO. Despite PwO with FA had greater basal BMI and fat mass, semaglutide showed similar results compared to PwO without FA in terms of weight and fat mass loss at short term.

“Correlation does not Imply Causation”, while Psychotropic Drugs do cause Neurochemical Imbalances and Dysfunction of Neurotransmission

Mental health professionals often prescribe psychotropic drug to patients diagnosed with mental health illnesses under the premise that neurochemical imbalance is a cause of mental health disorders. In this paper we discuss reasons to believe that there is no scientific research which provides evidence that neurochemical imbalances or problems with neurotransmission in the brain are causative factors in the etiology of mental health illnesses. Behavioral and neurochemical research studies in animals show an ASSOCIATION between mental health states and alteration of neurotransmitter signaling. However, correlation does not imply causation. To the contrary, stress paradigms in rodents show a diminishing of the activity of the mesolimbic dopaminergic reward pathway _as a result of_ long-term stressful stimuli. Furthermore, studies in human cases of mental health disorders show that psychotropic drugs cause disturbances in neurotransmission or neurochemical homeostasis as seen in biochemical research studies, and this is manifest by the behavioral consequences experienced during withdrawal in humans and animals. SIGNIFICANCE: This paper presents reasons to question the safety and efficacy of the common use of psychotropic drugs in the mental health industry.

Familial effects account for association between chronic pain and past month smoking.

Smoking is associated with chronic pain, but it is not established whether smoking causes pain or if the link is due to familial effects. One proposed mechanism is that smoking strengthens maladaptive cortico-striatal connectivity, which contributes to pain chronification. We leveraged a twin design to assess direct effects of smoking on pain controlling for familial confounds, and whether cortico-striatal connectivity mediates this association. In a population-based sample of 692 twins (age = 28.83 years), we assessed past-month smoking frequency (n = 132 used in the past month), presence and severity of a current pain episode (n = 179 yes), and resting-state functional connectivity of the nucleus accumbens and medial prefrontal cortex (NAc-mPFC). Smoking was significantly associated with pain, but the association was not significantly mediated by NAc-mPFC connectivity. In a co-twin control model, smoking predicted which families had more pain but could not distinguish pain between family members. Pain risk was 43% due to additive genetic (A) and 57% due to non-shared environmental (E) influences. Past-month smoking frequency was 71% genetic and 29% non-shared environmental. Smoking and pain significantly correlated phenotypically (r = 0.21, p = 0.001) and genetically (rg = 0.51, p < 0.001), but not environmentally (re = -0.18, p = 0.339). Pain and smoking are associated; however, the association appears to reflect shared familial risk factors, such as genetic risk, rather than being causal in nature. The connectivity strength of the reward pathway was not related to concurrent pain and smoking in this sample. Smoking does not appear to directly cause chronic pain; rather, there may be shared biopsychosocial risk factors, including genetic influences, that explain their association. These findings can be integrated into future research to identify shared biological pathways of both chronic pain and smoking behaviours as a way to conceptualize pain chronification.

Brain reward function in people who use cannabis: a systematic review.

Cannabis is one of the most widely used psychoactive substances globally. Cannabis use can be associated with alterations of reward processing, including affective flattening, apathy, anhedonia, and lower sensitivity to natural rewards in conjunction with higher sensitivity to cannabis-related rewards. Such alterations have been posited to be driven by changes in underlying brain reward pathways, as per prominent neuroscientific theories of addiction. Functional neuroimaging (fMRI) studies have examined brain reward function in cannabis users via the monetary incentive delay (MID) fMRI task; however, this evidence is yet to be systematically synthesised. We aimed to systematically integrate the evidence on brain reward function in cannabis users examined by the MID fMRI task; and in relation to metrics of cannabis exposure (e.g., dosage, frequency) and other behavioural variables. We pre-registered the review in PROSPERO and reported it using PRISMA guidelines. Literature searches were conducted in PsycINFO, PubMed, Medline, CINAHL, and Scopus. Nine studies were included, comprising 534 people with mean ages 16-to-28 years, of which 255 were people who use cannabis daily or almost daily, and 279 were controls. The fMRI literature to date led to largely non-significant group differences. A few studies reported group differences in the ventral striatum while participants anticipated rewards and losses; and in the caudate while participants received neutral outcomes. A few studies examined correlations between brain function and withdrawal, dosage, and age of onset; and reported inconsistent findings. There is emerging but inconsistent evidence of altered brain reward function in cannabis users examined with the MID fMRI task. Future fMRI studies are required to confirm if the brain reward system is altered in vulnerable cannabis users who experience a Cannabis Use Disorder, as postulated by prominent neuroscientific theories of addiction.

Histone Methyltransferase G9a Plays an Essential Role on Nicotine Preference in Zebrafish.

Psychostimulants regulate behavioral responses in zebrafish via epigenetic mechanisms. We have previously shown that DNA methylation and histone deacetylase (HDAC) inhibition abolish nicotine-induced conditioned place preference (CPP) but little is known about the role of histone methylation in addictive-like behaviors. To assess the influence of histone methylation on nicotine-CPP, zebrafish were treated with a histone (H3) lysine-9 (K9) dimethyltransferase G9a/GLP inhibitor, BIX-01294 (BIX), which was administered before conditioning sessions. We observed a dual effect of the inhibitor BIX: at high doses inhibited while at low doses potentiated nicotine reward. Transcriptional expression of α6 and α7 subunits of the nicotinic acetylcholine receptor and of G9a, DNA methyl transferase-3, and HDAC-1 was upregulated in zebrafish with positive scores for nicotine-CPP. Changes in relative levels of these mRNA molecules reflected the effects of BIX on nicotine reward. BIX treatment per sé did not affect transcriptional levels of epigenetic enzymes that regulate trimethylation or demethylation of H3. BIX reduced H3K9me2 protein levels in a dose-dependent manner in key structures of the reward pathway. Thus, our findings indicated that different doses of BIX differentially affect nicotine CPP via strong or weak inhibition of G9a/GLP activity. Additionally, we found that the lysine demethylase inhibitor daminozide abolished nicotine-CPP and drug seeking. Our data demonstrate that H3 methylation catalyzed by G9a/GLP is involved in nicotine-CPP induction. Dimethylation of K9 at H3 is an important epigenetic modification that should be considered as a potential therapeutic target to treat nicotine reward and perhaps other drug addictions.

Dorsal hippocampus to nucleus accumbens projections drive reinforcement via activation of accumbal dynorphin neurons

The hippocampus is pivotal in integrating emotional processing, learning, memory, and reward-related behaviors. The dorsal hippocampus (dHPC) is particularly crucial for episodic, spatial, and associative memory, and has been shown to be necessary for context- and cue-associated reward behaviors. The nucleus accumbens (NAc), a central structure in the mesolimbic reward pathway, integrates the salience of aversive and rewarding stimuli. Despite extensive research on dHPC→NAc direct projections, their sufficiency in driving reinforcement and reward-related behavior remains to be determined. Our study establishes that activating excitatory neurons in the dHPC is sufficient to induce reinforcing behaviors through its direct projections to the dorso-medial subregion of the NAc shell (dmNAcSh). Notably, dynorphin-containing neurons specifically contribute to dHPC-driven reinforcing behavior, even though both dmNAcSh dynorphin- and enkephalin-containing neurons are activated with dHPC stimulation. Our findings unveil a pathway governing reinforcement, advancing our understanding of the hippocampal circuity’s role in reward-seeking behaviors.

Neuronal Excitability in the Medial Habenula and Ventral Tegmental Area Is Differentially Modulated by Nicotine Dosage and Menthol in a Sex-Specific Manner.

The medial habenula (MHb) has been identified as the limiting factor for nicotine intake and facilitating nicotine withdrawal. However, few studies have assessed MHb neuronal excitability in response to nicotine, and, currently, a gap in knowledge is present for finding behavioral correlates to neuronal excitability in the region. Moreover, no study to date has evaluated sex or nicotine dosage as factors of excitability in the MHb. Here, we utilized an e-vape self-administration (EVSA) model to determine differences between sexes with different nicotine dosages ± menthol. Following this paradigm, we employed patch-clamp electrophysiology to assess key metrics of MHb neuronal excitability in relation to behavioral endpoints. We observed female mice self-administered significantly more than males, regardless of dosage. We also observed a direct correlation between self-administration behavior and MHb excitability with low-dose nicotine + menthol in males. Conversely, a high dose of nicotine ± menthol yields an inverse correlation between excitability and self-administration behavior in males only. In addition, intrinsic excitability in the ventral tegmental area (VTA) does not track with the amount of nicotine self-administered. Rather, they correlate to the active/inactive discrimination of mice. Using fast-scan cyclic voltammetry, we also observed that dopamine release dynamics are linked to reinforcement-related behavior in males and motivation-related behaviors in females. These results point to a sex-specific difference in the activity of the MHb and VTA leading to distinct differences in self-administration behavior. His could lend evidence to clinical observations of smoking and nicotine-use behavior differing between males and females.

Evaluation of Effects of Food Addiction in Rat Model: An Experimental Study

Introduction: Palatable foods have potent reinforcing effects that are mediated, partly, by an abrupt augmentation of dopaminergic neurotransmitters in the brain’s reward pathways. Food addiction to highly palatable foods contributes to the increasing prevalence of obesity. Aim: To evaluate the effect of food addiction on neurobehavioural parameters and the Behavioral Satiety Sequence (BSS) during restriction to a highly palatable diet in a food addiction rat model. Materials and Methods: The experimental study was conducted in the Pharmacology Department at PSG Institute of Medical Sciences and Research, Coimbatore, Tamil Nadu, India from April 2018 to January 2019. The study included six animals out of 28 female Sprague Dawley rats aged approximately 10 weeks and weighing 180-220 g were allocated to the control group and were fed a Standard Chow diet (SC) throughout the study. Twenty-two animals (induction group) were exposed to free choice between SC and a highly palatable Cafeteria Diet (CD), a mix of equal amounts of Bounty®, Snickers®, Mars®, and Milka® chocolate made into homogenous food pellets. After six weeks, 12 animals were randomly selected to have restricted access to the CD diet with free access to SC, while the rest continued to receive a free choice between the two diets for two weeks. Central Nervous System (CNS) parameters, BSS, 24-hour food intake, and body weight were recorded. Results: A significant decrease of 25.4 seconds (18.27%) in the mean time the CD restricted group stayed on the rotarod (113.6±8.31) seconds. and a reduced locomotor activity score of 46.92 (20.94%) in the CD access group in the actophotometer (177.08±5.29) compared to SC was noted. In the open field test, the CD restricted group demonstrated a 47.33% increase in grooming (12.0±1.11) and a 30% lower number of central squares crossed (2.80±0.57). In the Elevated Plus Maze (EPM), the time spent in the open arm (15.00±8.10) was statistically lower (p=0.045). No statistically significant difference between groups was recorded in the forced swim or tail suspension tests. Disruption of the BSS in varying dimensions was apparent in both CD groups. Conclusion: The study has shown that anxiety and altered feeding behaviour were evident in the CD restricted rats in the food addiction model.

The Neuroscience of Music Processing and Music Interventions for Mental Illness

Growing research on music and language processing in recent years has simultaneously enabled us to understand its uses and promise in therapeutic settings. This review used recently published peer-reviewed literature to study the neurobiology of music processing, which includes the auditory processing hierarchy and engagement with language processes. Results showed that music has an impact on emotion systems, particularly the reward pathway and the Hypothalamic-Pituitary-Adrenal (HPA) axis. Furthermore, listening to music or music therapy for the treatment of psychiatric and neurological diseases demonstrated effectiveness in improving patient outcomes. Overall, music processing is a sophisticated process with some similarities to language processing. Future randomized controlled trials are required to shed light on the neurocognitive aspect of music processing.

A Review on Neuroesthetics and Neurosart

Man has always felt different and special from other living things in the universe he lives in. He makes sense of the world he lives in, thinks about it, and brings theories and explanations about existence. He wants to be freed from his impulses, he rejects his animal nature. For example, if he is making love, it is out of love. While this whole point of view does not make man as free as a cat in living his impulsiveness, man is nevertheless willing to separate his animal nature from other species with thick lines by means of art and aesthetics. Because to the extent that art and aesthetics distance people from their predatory nature, they will provide safe spaces for them. Since the pictures he drew on the cave walls, he is now on a higher level dominating nature. He will not eat every dish that is put in front of him, for example, he will look for artistic touches. With all these aspects, it would not be wrong to say that art and aesthetics have a very old history. As in almost every subject, art and aesthetics also have points in terms of neuroscience. In this sense, Neuroesthetics and Neuroart provides explanations about the nature of human, art and aesthetics. It explores how the enormous synaptic connections, the neuroplastic brain, reach a line of transformation with artistic and aesthetic stimuli. In our study, we will focus on the contribution of art and artistic stimuli to the simultaneous development of the right and left brain, especially to the orbito prontal part of the brain. However, within the scope of neuroaesthetics, the effects of aesthetics on the nucleus accumbens (reward center) as well as the effects of art on the release of the happiness hormone oxytocin and its beneficial reducing effect on mental disorders such as depression will be emphasized. In addition, the differences in the amygdala region of the brain in syndromes such as autism, unlike healthy groups, and the outcomes of this difference in the artistic field will be discussed. In addition to all these, emphasis will be placed on early diagnosis methods of diseases such as stroke and Alzheimer’s through artistic works. In creating this review article, publications of refereed journals published in fields such as Google Academy, master’s and doctoral theses published in national and international thesis centers, and some books and additional resources published in the field of neuroaestheticsneuroart were used methodologically. In our related study, experimental designs made in this sense will be included in the literature and theories on the indispensability of art and aesthetics for human nature will be included.

The Social Dilemma: Social media and mental health

Human beings are social creatures that require thecompanionship of others to make progress in life. Thus,being socially connected with other people can relievestress, anxiety, and sadness, but lack of social connectioncan pose serious risks to mental health.1 Social mediahas recently become part of people’s daily activities;many of them spend hours each day on Messenger,Instagram, Facebook, and other popular social media andmany scholars studied the impact of social media andapplications on various aspects of people’s lives. The advent of the digital age has led to changes in themanner and nature of information generation, circulation,and reception. For example, social media connects peoplethrough text, pictures, and videos to build a vast socialnetwork and significantly influence people’s mindset andbehaviors.3 Social media has a reinforcing nature. Using itactivates the brain’s reward center by releasing dopaminelinked to pleasurable activities such as sex, food, andsocial interaction. The platforms are designed to beaddictive and are associated with anxiety, depression andeven physical ailments. FOMO—fear of missing out—also plays a role. If everyone else is using social mediasites, and if someone doesn’t join in, there’s concern thatthey’ll miss jokes, connections, or invitations. Missingexperiences can create anxiety and depression. Whenpeople look online and see they’re excluded from anactivity, it can affect thoughts and feelings, and can affectthem physically. A 2018 British study tied social mediause to decreased, disrupted, and delayed sleep, whichis associated with depression, memory loss, and pooracademic performance. Social media use can affect users’physical health even more directly

Alcohol and the dopamine system.

The mesolimbic dopamine pathway plays a major role in drug reinforcement and is likely involved also in the development of drug addiction. Ethanol, like most addictive drugs, acutely activates the mesolimbic dopamine system and releases dopamine, and ethanol-associated stimuli also appear to trigger dopamine release. In addition, chronic exposure to ethanol reduces the baseline function of the mesolimbic dopamine system. The molecular mechanisms underlying ethanol´s interaction with this system remain, however, to be unveiled. Here research on the actions of ethanol in the mesolimbic dopamine system, focusing on the involvement of cystein-loop ligand-gated ion channels, opiate receptors, gastric peptides and acetaldehyde is briefly reviewed. In summary, a great complexity as regards ethanol´s mechanism(s) of action along the mesolimbic dopamine system has been revealed. Consequently, several new targets and possibilities for pharmacotherapies for alcohol use disorder have emerged.

Opioidergic signaling contributes to food-mediated suppression of AgRP neurons

Opioids are generally known to promote hedonic food consumption. Although much of the existing evidence is primarily based on studies of the mesolimbic pathway, endogenous opioids and their receptors are widely expressed in hypothalamic appetite circuits as well; however, their role in homeostatic feeding remains unclear. Using a fluorescent opioid sensor, deltaLight, here we report that mediobasal hypothalamic opioid levels increase by feeding, which directly and indirectly inhibits agouti-related protein (AgRP)-expressing neurons through the μ-opioid receptor (MOR). AgRP-specific MOR expression increases by energy surfeit and contributes to opioid-induced suppression of appetite. Conversely, its antagonists diminish suppression of AgRP neuron activity by food and satiety hormones. Mice with AgRP neuron-specific ablation of MOR expression have increased fat preference without increased motivation. These results suggest that post-ingestion release of endogenous opioids contributes to AgRP neuron inhibition to shape food choice through MOR signaling.

Changes in the dopaminergic circuitry and adult neurogenesis linked to reinforcement learning in corvids.

The caudolateral nidopallium (NCL, an analog of the prefrontal cortex) is known to be involved in learning, memory, and discrimination in corvids (a songbird), whereas the involvement of other brain regions in these phenomena is not well explored. We used house crows (Corvus splendens) to explore the neural correlates of learning and decision-making by initially training them on a shape discrimination task followed by immunohistochemistry to study the immediate early gene expression (Arc), a dopaminoceptive neuronal marker (DARPP-32, Dopamine- and cAMP-regulated phosphoprotein, Mr 32 kDa) to understand the involvement of the reward pathway and an immature neuronal marker (DCX, doublecortin) to detect learning-induced changes in adult neurogenesis. We performed neuronal counts and neuronal tracing, followed by morphometric analyses. Our present results have demonstrated that besides NCL, other parts of the caudal nidopallium (NC), avian basal ganglia, and intriguingly, vocal control regions in house crows are involved in visual discrimination. We have also found that training on the visual discrimination task can be correlated with neurite pruning in mature dopaminoceptive neurons and immature DCX-positive neurons in the NC of house crows. Furthermore, there is an increase in the incorporation of new neurons throughout NC and the medial striatum which can also be linked to learning. For the first time, our results demonstrate that a combination of structural changes in mature and immature neurons and adult neurogenesis are linked to learning in corvids.

Evaluation of White Matter and Cerebellum Structures of Essential Tremor and Parkinson's Patients by Diffusion Tensor Imaging and Volbrain Method

Essential tremor (ET) and Parkinson's disease (PD) are the two most commonly encountered tremor disorders in movement disorders. Diffusion tensor imaging (DTI) is one of the best in vivo ways of mapping white matter pathways in the human brain. The aim of our study was to investigate diffusion variables and cerebellum volume in ET and PD using parcellation methods. Our study included 20 ET, 20 PD and 20 healthy controls. Fraction Anisotropy (FA) and Mean Diffusivity (MD) values were obtained with DTI, while the volume of each lobe of the cerebellum was obtained with T1 images. One-way ANOVA was used for intergroup analysis and Scheffe test was used for post-hoc analysis. Significant differences were found in the diffusion values of the pedunculus cerebellaris, fornix stria, superior longitudinal fasciculus, sagittal stratum, cerebral pedunculus, tapatum and thalamus of ET and PD. Lobule V, Lobule IX, Lobule X volumes of the cerebellum showed significant differences between the groups. Stria thermialis shows involvement of mesolimbic dopaminergic system in PD and it is thought that disruption of strial networks leads to changes in the activity of cerebellar networks and reveals the role of the cerebellum in tremor. It is obvious that cerebellar thalamocortical pathways are affected in Parkinson's disease. In Parkinson's disease, patients should be evaluated for visual processing, conceptualisation, postural instability and gait disturbance to clarify the diagnosis or to differentiate from essential tremor.