The dopamine theory of addiction: 40 years of highs and lows

Nature reviews. Neuroscience, Journal Year: 2015, Volume and Issue: 16(5), P. 305 - 312

Published: April 15, 2015

Language: Английский

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Dopamine System Dysregulation in Major Depressive Disorders

The International Journal of Neuropsychopharmacology, Journal Year: 2017, Volume and Issue: 20(12), P. 1036 - 1046

Published: June 28, 2017

Anhedonia is considered a core feature of major depressive disorder, and the dopamine system plays pivotal role in hedonic deficits described this disorder. Dopaminergic activity complex under regulation multiple brain structures, including ventral subiculum hippocampus basolateral amygdala. Whereas basic clinical studies demonstrate dopaminergic depression, origin these likely lies dysregulation its regulatory afferent circuits. This review explores current information regarding modulation relevance to as well some system-level effects novel antidepressants such agomelatine ketamine.

Language: Английский

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Insulin Action in Brain Regulates Systemic Metabolism and Brain Function

Diabetes, Journal Year: 2014, Volume and Issue: 63(7), P. 2232 - 2243

Published: June 14, 2014

Insulin receptors, as well IGF-1 receptors and their postreceptor signaling partners, are distributed throughout the brain. acts on these to modulate peripheral metabolism, including regulation of appetite, reproductive function, body temperature, white fat mass, hepatic glucose output, response hypoglycemia. also modulates neurotransmitter channel activity, brain cholesterol synthesis, mitochondrial function. Disruption insulin action in leads impairment neuronal function synaptogenesis. In addition, phosphorylation tau protein, an early component development Alzheimer disease. Thus, alterations can contribute metabolic syndrome, mood disorders neurodegenerative diseases.

Language: Английский

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VTA dopaminergic neurons regulate ethologically relevant sleep–wake behaviors

Nature Neuroscience, Journal Year: 2016, Volume and Issue: 19(10), P. 1356 - 1366

Published: Sept. 5, 2016

Language: Английский

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Prefrontal cortical regulation of brainwide circuit dynamics and reward-related behavior

Science, Journal Year: 2015, Volume and Issue: 351(6268)

Published: Dec. 31, 2015

Motivation for reward drives adaptive behaviors, whereas impairment of perception and experience (anhedonia) can contribute to psychiatric diseases, including depression schizophrenia. We sought test the hypothesis that medial prefrontal cortex (mPFC) controls interactions among specific subcortical regions govern hedonic responses. By using optogenetic functional magnetic resonance imaging locally manipulate but globally visualize neural activity in rats, we found dopamine neuron stimulation striatal activity, increased mPFC excitability reduces this response inhibits behavioral drive dopaminergic stimulation. This chronic overactivity also stably suppresses natural reward-motivated behaviors induces new brainwide interactions, which predict degree anhedonia individuals. These findings describe a mechanism by modulates expression reward-seeking behavior, regulating dynamical between distant regions.

Language: Английский

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How Might Circadian Rhythms Control Mood? Let Me Count the Ways...

Biological Psychiatry, Journal Year: 2013, Volume and Issue: 74(4), P. 242 - 249

Published: April 1, 2013

Language: Английский

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Enhancing Depression Mechanisms in Midbrain Dopamine Neurons Achieves Homeostatic Resilience

Science, Journal Year: 2014, Volume and Issue: 344(6181), P. 313 - 319

Published: April 17, 2014

Typical therapies try to reverse pathogenic mechanisms. Here, we describe treatment effects achieved by enhancing depression-causing mechanisms in ventral tegmental area (VTA) dopamine (DA) neurons. In a social defeat stress model of depression, depressed (susceptible) mice display hyperactivity VTA DA neurons, caused an up-regulated hyperpolarization-activated current (I(h)). Mice resilient stress, however, exhibit stable normal firing these Unexpectedly, had even larger I(h), which was observed parallel with increased potassium (K(+)) channel currents. Experimentally further Ih or optogenetically increasing the neurons susceptible completely reversed depression-related behaviors, antidepressant effect through resilience-like, projection-specific homeostatic plasticity. These results indicate potential therapeutic path promoting natural resilience for depression treatment.

Language: Английский

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The dopamine hypothesis of bipolar affective disorder: the state of the art and implications for treatment

Molecular Psychiatry, Journal Year: 2017, Volume and Issue: 22(5), P. 666 - 679

Published: March 14, 2017

Bipolar affective disorder is a common neuropsychiatric disorder. Although its neurobiological underpinnings are incompletely understood, the dopamine hypothesis has been key theory of pathophysiology both manic and depressive phases illness for over four decades. The increased use antidopaminergics in treatment this new vivo neuroimaging post-mortem studies makes it timely to review theory. To do this, we conducted systematic search post-mortem, pharmacological, functional magnetic resonance molecular imaging function bipolar Converging findings from pharmacological support that state hyperdopaminergia, specifically elevations D2/3 receptor availability hyperactive reward processing network, underlies mania. In depression show transporter levels, but changes other aspects dopaminergic inconsistent. Puzzlingly, evidence shows agonists can improve symptoms perhaps actions at receptors may reconcile these findings. Tentatively, suggests model where an elevation striatal would lead neurotransmission mania, whilst (DAT) levels reduced depression. Thus, be speculated failure homoeostasis might underlie limitations include reliance on evidence, as could potentially affect monoamines, scarcity function. This model, if confirmed, implications developing strategies such reducing synthesis and/or release mania DAT blockade

Language: Английский

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Divergent Routing of Positive and Negative Information from the Amygdala during Memory Retrieval

Neuron, Journal Year: 2016, Volume and Issue: 90(2), P. 348 - 361

Published: April 1, 2016

Language: Английский

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Insulin resistance in brain alters dopamine turnover and causes behavioral disorders

Proceedings of the National Academy of Sciences, Journal Year: 2015, Volume and Issue: 112(11), P. 3463 - 3468

Published: March 2, 2015

Diabetes and insulin resistance are associated with altered brain imaging, depression, increased rates of age-related cognitive impairment. Here we demonstrate that mice a brain-specific knockout the receptor (NIRKO mice) exhibit mitochondrial dysfunction reduced oxidative activity, levels reactive oxygen species, lipid protein oxidation in striatum nucleus accumbens. NIRKO also monoamine oxidase A B (MAO B) leading to dopamine turnover these areas. Studies cultured neurons glia cells indicate changes MAO direct consequence loss signaling. As result, develop anxiety depressive-like behaviors can be reversed by treatment inhibitors, as well tricyclic antidepressant imipramine, which inhibits activity reduces stress. Thus, induces dopaminergic behaviors, demonstrating potential molecular link between central behavioral disorders.

Language: Английский

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