Biological psychiatry
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Biological psychiatry · Jul 2013
Opposing catecholamine changes in the bed nucleus of the stria terminalis during intracranial self-stimulation and its extinction.
While studies suggest that both dopamine and norepinephrine neurotransmission support reinforcement learning, the role of dopamine has been emphasized. As a result, little is known about norepinephrine signaling during reward learning and extinction. Both dopamine and norepinephrine projections innervate distinct regions of the bed nucleus of the stria terminalis (BNST), a structure that mediates behavioral and autonomic responses to stress and anxiety. We investigated whether norepinephrine release in the ventral BNST (vBNST) and dopamine release in the dorsolateral BNST (dlBNT) correlate with reward learning during intracranial self-stimulation (ICSS). ⋯ The data demonstrate that norepinephrine release in the vBNST differs from dopamine release in the dlBNST and the NAc in that it signals the absence of reward rather than responding to reward predictive cues.
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Biological psychiatry · Jun 2013
ReviewRapid-acting glutamatergic antidepressants: the path to ketamine and beyond.
Traditional antidepressants require many weeks to reveal their therapeutic effects. However, the widely replicated observation that a single subanesthetic dose of the N-methyl-D-aspartate glutamate receptor antagonist ketamine produced meaningful clinical improvement within hours, suggested that rapid-acting antidepressants might be possible. The ketamine studies stimulated a new generation of basic antidepressant research that identified new neural signaling mechanisms in antidepressant response and provided a conceptual framework linking a group of novel antidepressant mechanisms. This article presents the path that led to the testing of ketamine, considers its promise as an antidepressant, and reviews novel treatment mechanisms that are emerging from this line of research.
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Biological psychiatry · Jun 2013
Clinical TrialNeural correlates of rapid antidepressant response to ketamine in treatment-resistant unipolar depression: a preliminary positron emission tomography study.
Multiple lines of evidence support a role for the glutamatergic system in the pathophysiology of major depressive disorder (MDD). Ketamine, an N-methyl-D-aspartate antagonist, rapidly improves depressive symptoms in individuals with treatment-resistant depression. The neural mechanisms underlying this effect remain unknown. ⋯ Although preliminary, these results indicate that treatment-resistant MDD subjects showed decreased metabolism in the right habenula and the extended medial and orbital prefrontal networks in association with rapid antidepressant response to ketamine. Conversely, metabolism increased in sensory association cortices, conceivably related to the illusory phenomena sometimes experienced with ketamine. Further studies are needed to elucidate how these functional anatomical changes relate to the molecular mechanisms underlying ketamine's rapid antidepressant effects.
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Biological psychiatry · Jun 2013
Rapid remission of conditioned fear expression with extinction training paired with vagus nerve stimulation.
Fearful experiences can produce long-lasting and debilitating memories. Extinction of conditioned fear requires consolidation of new memories that compete with fearful associations. In human subjects, as well as rats, posttraining stimulation of the vagus nerve enhances memory consolidation. Subjects with posttraumatic stress disorder show impaired extinction of conditioned fear. The objective of this study was to determine whether vagus nerve stimulation (VNS) can enhance the consolidation of extinction of conditioned fear. ⋯ Extinction paired with VNS is more rapid than extinction paired with sham stimulation. As it is currently approved by the Federal Food and Drug Administration for depression and seizure prevention, VNS is a readily available and promising adjunct to exposure therapy for the treatment of severe anxiety disorders.
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Biological psychiatry · May 2013
Sweetened-fat intake sensitizes gamma-aminobutyric acid-mediated feeding responses elicited from the nucleus accumbens shell.
There is much interest in exploring whether reward-driven feeding can produce druglike plasticity in the brain. The gamma-aminobutyric acid (GABA) system in the nucleus accumbens (Acb) shell, which modulates hypothalamic feeding systems, is well placed to "usurp" homeostatic control of feeding. Nevertheless, it is unknown whether feeding-induced neuroadaptations occur in this system. ⋯ Palatable feeding engenders hypersensitivity of Acb shell GABA responses; this effect may involve feeding-induced release of opioid peptides. Heightened arousal, aversive experiences, or increased catecholamine transmission alone are insufficient to produce the effect, and a hunger-induced feeding drive is insufficient to reveal the effect. These findings reveal a novel type of food-induced neuroadaptation within the Acb; possible implications for understanding crossover effects between food reward and drug reward are discussed.