scholarly journals Dopaminergic learning and arousal circuits mediate opposing effects on alcohol consumption in Drosophila

2019 ◽  
Author(s):  
Shamsideen A. Ojelade ◽  
Andrew R. Butts ◽  
Collin B. Merrill ◽  
Eve Privman Champaloux ◽  
Yoshinori Aso ◽  
...  
Keyword(s):  
Alcohol Consumption ◽  
Drugs Of Abuse ◽  
Dopamine Neurons ◽  
Mushroom Bodies ◽  
Drug Reinforcement ◽  
Bilateral Pair ◽  
Opposing Effects ◽  
Dopaminergic Pathways ◽  
The Brain

AbstractThe response to drugs of abuse is a combination of aversive and reinforcing reactions. While much is known about the role of dopamine in mammalian drug reinforcement, we know little about the brain circuits mediating drug aversion. Here we show that two distinct dopaminergic circuits mediate reinforcing and acute aversive responses to alcohol consumption in Drosophila. Protocerebral anterior medial dopamine neurons projecting to the mushroom bodies are required for flies to acquire alcohol preference. Conversely, a bilateral pair of dopamine neurons projecting to the dorsal fan-shaped body (dFSB) mediates acute alcohol avoidance. Alcohol consumption can be reduced by decreasing the activity of the appetitive reinforcement-circuit to the mushroom bodies, or by increasing activity in the dopamine neurons projecting to the dFSB. Thus, distinct dopaminergic pathways can be targeted to reduce the intake of harmful drugs.

scholarly journals Role of Descending Dopaminergic Pathways in Pain Modulation

2019 ◽  
Vol 17 (12) ◽  
pp. 1176-1182 ◽  
Author(s):  
Changsheng Li ◽  
Sufang Liu ◽  
Xihua Lu ◽  
Feng Tao
Keyword(s):  
Chronic Pain ◽  
Well Being ◽  
Pain Modulation ◽  
Central Regulation ◽  
Dopaminergic Systems ◽  
Different Types ◽  
Dopaminergic Pathways ◽  
The Brain

Pain, especially when chronic, is a common reason patients seek medical care and it affects the quality of life and well-being of the patients. Unfortunately, currently available therapies for chronic pain are often inadequate because the neurobiological basis of such pain is still not fully understood. Although dopamine has been known as a neurotransmitter to mediate reward and motivation, accumulating evidence has shown that dopamine systems in the brain are also involved in the central regulation of chronic pain. Most importantly, descending dopaminergic pathways play an important role in pain modulation. In this review, we discuss dopamine receptors, dopaminergic systems in the brain, and the role of descending dopaminergic pathways in the modulation of different types of pain.

scholarly journals Inhibition in Multiclass Classification

2012 ◽  
Vol 24 (9) ◽  
pp. 2473-2507 ◽  
Author(s):  
Ramón Huerta ◽  
Shankar Vembu ◽  
José M. Amigó ◽  
Thomas Nowotny ◽  
Charles Elkan
Keyword(s):  
Support Vector ◽  
Mushroom Bodies ◽  
Data Sets ◽  
Tight Bound ◽  
Multiclass Support Vector Machine ◽  
Output Neurons ◽  
Multiclass Svm ◽  
Leave One Out ◽  
The Brain

The role of inhibition is investigated in a multiclass support vector machine formalism inspired by the brain structure of insects. The so-called mushroom bodies have a set of output neurons, or classification functions, that compete with each other to encode a particular input. Strongly active output neurons depress or inhibit the remaining outputs without knowing which is correct or incorrect. Accordingly, we propose to use a classification function that embodies unselective inhibition and train it in the large margin classifier framework. Inhibition leads to more robust classifiers in the sense that they perform better on larger areas of appropriate hyperparameters when assessed with leave-one-out strategies. We also show that the classifier with inhibition is a tight bound to probabilistic exponential models and is Bayes consistent for 3-class problems. These properties make this approach useful for data sets with a limited number of labeled examples. For larger data sets, there is no significant comparative advantage to other multiclass SVM approaches.

Deep brain stimulation of the nucleus accumbens reduces alcohol intake in alcohol-preferring rats

2010 ◽  
Vol 29 (2) ◽  
pp. E12 ◽  
Author(s):  
Michael B. Henderson ◽  
Alan I. Green ◽  
Perry S. Bradford ◽  
David T. Chau ◽  
David W. Roberts ◽  
...  
Keyword(s):  
Deep Brain Stimulation ◽  
Nucleus Accumbens ◽  
Alcohol Consumption ◽  
Brain Stimulation ◽  
Alcohol Intake ◽  
Drugs Of Abuse ◽  
Alcohol Preference ◽  
Stable Pattern ◽  
Deep Brain

Object The authors tested the hypothesis that deep brain stimulation (DBS) in the nucleus accumbens (NAcc) decreases alcohol intake in alcohol-preferring (P) rats after each animal has established a stable, large alcohol intake and after P rats with an established intake have been deprived of alcohol for 4–6 weeks. Methods Bipolar stimulating electrodes were bilaterally placed in the NAcc using stereotactic coordinates. In the first study, P rats (9 animals) were allowed to establish a stable pattern of alcohol intake (about 5–7 g/day) over approximately 2 weeks, and the acute effects of DBS in the NAcc (140–150 Hz, 60-μsec pulse width, and 200-μA current intensity) on alcohol intake and alcohol preference were studied. Each animal acted as its own control and received 1 hour of DBS followed by 1 hour of sham-DBS or vice versa on each of 2 sequential days. The order of testing (sham-DBS vs DBS) was randomized. In the second study, each animal was allowed to establish a stable alcohol intake and then the animal was deprived of alcohol for 4–6 weeks. Animals received DBS (6 rats) or sham-DBS (5 rats) in the NAcc for 24 hours starting when alcohol was reintroduced to each animal. Results Deep brain stimulation in the NAcc, as compared with a period of sham-DBS treatment in the same animals, acutely decreased alcohol preference. Furthermore, alcohol consumption and preference were significantly reduced in the DBS group compared with the sham treatment group during the first 24 hours that alcohol was made available after a period of forced abstinence. Conclusions The NAcc plays a key role in the rewarding and subsequent addictive properties of drugs of abuse in general and of alcohol in particular. Deep brain stimulation in the NAcc reduced alcohol consumption in P rats both acutely and after a period of alcohol deprivation. Therefore, DBS in the NAcc coupled with other neurophysiological measurements may be a useful tool in determining the role of the NAcc in the mesocorticolimbic reward circuit. Deep brain stimulation in the NAcc may also be an effective treatment for reducing alcohol consumption in patients who abuse alcohol and have not responded to other forms of therapy.

scholarly journals The Role of Alcohol Metabolism in the Pathology of Alcohol Hangover

2020 ◽  
Vol 9 (11) ◽  
pp. 3421 ◽  
Author(s):  
Marlou Mackus ◽  
Aurora JAE van de Loo ◽  
Johan Garssen ◽  
Aletta D. Kraneveld ◽  
Andrew Scholey ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Alcohol Consumption ◽  
Significant Negative Correlation ◽  
Ethanol Metabolism ◽  
Alcohol Metabolism ◽  
Alcohol Hangover ◽  
The Brain ◽  
And Oxidative Stress ◽  
Biomarkers Of Oxidative Stress

The limited number of available studies that examined the pathology of alcohol hangover focused on biomarkers of alcohol metabolism, oxidative stress and the inflammatory response to alcohol as potentially important determinants of hangover severity. The available literature on alcohol metabolism and oxidative stress is reviewed in this article. The current body of evidence suggests a direct relationship between blood ethanol concentration and hangover severity, whereas this association is not significant for acetaldehyde. The rate of alcohol metabolism seems to be an important determinant of hangover severity. That is, fast elimination of ethanol is associated with experiencing less severe hangovers. An explanation for this observation may be the fact that ethanol—in contrast to acetaldehyde—is capable of crossing the blood–brain barrier. With slower ethanol metabolism, more ethanol is able to reach the brain and elicit hangover symptoms. Hangover severity was also significantly associated with biomarkers of oxidative stress. More oxidative stress in the first hours after alcohol consumption was associated with less severe next-day hangovers (i.e., a significant negative correlation was found between hangover severity and malondialdehyde). On the contrary, more oxidative stress at a later stage after alcohol consumption was associated with having more severe next-day hangovers (i.e., a significant positive correlation was found between hangover severity and 8-isoprostane). In conclusion, assessment of biomarkers of alcohol metabolism suggests that fast elimination of ethanol is associated with experiencing less severe hangovers. More research is needed to further examine the complex interrelationship between alcohol metabolism, the role of acetaldehyde and oxidative stress and antioxidants, and the pathology of the alcohol hangover.

Addiction (Oxford Psychiatry Library)

2018 ◽  
Author(s):  
David J. Nutt ◽  
Liam J. Nestor
Keyword(s):  
Drugs Of Abuse ◽  
Critical Role ◽  
Brain Disorder ◽  
Comprehensive Overview ◽  
Brain Science ◽  
Pharmacological Targets ◽  
Variable Nature ◽  
Reward Dependence ◽  
The Brain

Part of the Oxford Psychiatry Library series, this resource is a clear and comprehensive overview of the brain science underpinning addiction that helps explain the current and future therapeutics for the range of addictions, using full colour images to enhance understanding. It focuses on the nature of addiction as a brain disorder that includes a range of different behavioural traits such as impulsivity and reward dependence, and discusses the critical role of kinetic and pharmacological factors. The also explains how the primary pharmacological targets of drugs of abuse are now understood, the relation to the variable nature of addiction to different substances, and how this may lead to new approaches to treatment.

The Role of Mitochondria in the Genesis of Neuroaxonal Dystrophy in the Brains of Aging Mice

1975 ◽  
Vol 33 ◽  
pp. 372-373
Author(s):  
J.E. Johnson
Keyword(s):  
Electron Microscopy ◽  
Present Report ◽  
Light And Electron Microscopy ◽  
Dorsal Column ◽  
Neuroaxonal Dystrophy ◽  
Nucleus Gracilis ◽  
Dystrophic Axons ◽  
The Brain ◽  
Nucleus Cuneatus

Although neuroaxonal dystrophy (NAD) has been examined by light and electron microscopy for years, the nature of the components in the dystrophic axons is not well understood. The present report examines nucleus gracilis and cuneatus (the dorsal column nuclei) in the brain stem of aging mice.Mice (C57BL/6J) were sacrificed by aldehyde perfusion at ages ranging from 3 months to 23 months. Several brain areas and parts of other organs were processed for electron microscopy.At 3 months of age, very little evidence of NAD can be discerned by light microscopy. At the EM level, a few axons are found to contain dystrophic material. By 23 months of age, the entire nucleus gracilis is filled with dystrophic axons. Much less NAD is seen in nucleus cuneatus by comparison. The most recurrent pattern of NAD is an enlarged profile, in the center of which is a mass of reticulated material (reticulated portion; or RP).

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