Antidepressant Effect of Optogenetic Stimulation of the Medial Prefrontal Cortex

Journal of Neuroscience, Journal Year: 2010, Volume and Issue: 30(48), P. 16082 - 16090

Published: Dec. 1, 2010

Brain stimulation and imaging studies in humans have highlighted a key role for the prefrontal cortex clinical depression; however, it remains unknown whether excitation or inhibition of cortical neuronal activity is associated with antidepressant responses. Here, we examined cellular indicators functional activity, including immediate early genes (IEGs) zif268 ( egr1 ), c-fos , arc clinically depressed obtained postmortem. We also these ventral portion medial (mPFC) mice after chronic social defeat stress, mouse model depression. In addition, used viral vectors to overexpress channel rhodopsin 2 (a light-activated cation channel) mPFC optogenetically drive “burst” patterns firing vivo examine behavioral consequences. Prefrontal tissue derived from displayed significant reductions IEG expression, consistent deficit within this brain region. Mice subjected stress exhibited similar levels expression mPFC. Interestingly, some changes were not observed defeated that escape deleterious consequences i.e., resilient animals. those expressed strong depressive-like phenotype, susceptible animals, optogenetic exerted potent antidepressant-like effects, without affecting general locomotor anxiety-like behaviors, memory. These results indicate determinant depression-like behavior, as well

Language: Английский

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The Neuroscience of Drug Reward and Addiction

Physiological Reviews, Journal Year: 2019, Volume and Issue: 99(4), P. 2115 - 2140

Published: Sept. 11, 2019

Drug consumption is driven by a drug's pharmacological effects, which are experienced as rewarding, and influenced genetic, developmental, psychosocial factors that mediate drug accessibility, norms, social support systems or lack thereof. The reinforcing effects of drugs mostly depend on dopamine signaling in the nucleus accumbens, chronic exposure triggers glutamatergic-mediated neuroadaptations striato-thalamo-cortical (predominantly prefrontal cortical regions including orbitofrontal cortex anterior cingulate cortex) limbic pathways (amygdala hippocampus) that, vulnerable individuals, can result addiction. In parallel, changes extended amygdala negative emotional states perpetuate taking an attempt to temporarily alleviate them. Counterintuitively, addicted person, actual associated with attenuated increase brain reward regions, might contribute drug-taking behavior compensate for difference between magnitude expected triggered conditioning cues experience it. Combined, these enhanced motivation "seek drug" (energized increases cues) impaired top-down self-regulation favors compulsive against backdrop emotionality interoceptive awareness "drug hunger." Treatment interventions intended reverse show promise therapeutic approaches

Language: Английский

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The Nucleus Accumbens: Mechanisms of Addiction across Drug Classes Reflect the Importance of Glutamate Homeostasis

Pharmacological Reviews, Journal Year: 2016, Volume and Issue: 68(3), P. 816 - 871

Published: June 30, 2016

The nucleus accumbens is a major input structure of the basal ganglia and integrates information from cortical limbic structures to mediate goal-directed behaviors. Chronic exposure several classes drugs abuse disrupts plasticity in this region, allowing drug-associated cues engender pathologic motivation for drug seeking. A number alterations glutamatergic transmission occur within after withdrawal chronic exposure. These drug-induced neuroadaptations serve as molecular basis relapse vulnerability. In review, we focus on role that glutamate signal transduction plays addiction-related First, explore accumbens, including cell types neuronal populations present well afferent efferent connections. Next discuss rodent models addiction assess viability these testing candidate pharmacotherapies prevention relapse. Then provide review literature describing how synaptic altered also pharmacological manipulation systems can inhibit seeking laboratory setting. Finally, examine results clinical trials which designed manipulate have been effective treating human patients. Further elucidation alter will be necessary development new therapeutics treatment across all addictive substances.

Language: Английский

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Striatal circuits for reward learning and decision-making

Nature reviews. Neuroscience, Journal Year: 2019, Volume and Issue: 20(8), P. 482 - 494

Published: June 6, 2019

Language: Английский

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Differential Innervation of Direct- and Indirect-Pathway Striatal Projection Neurons

Neuron, Journal Year: 2013, Volume and Issue: 79(2), P. 347 - 360

Published: June 27, 2013

Language: Английский

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