Biological psychiatry
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Biological psychiatry · Oct 2013
Developmental disruption of gamma-aminobutyric acid function in the medial prefrontal cortex by noncontingent cocaine exposure during early adolescence.
Drug experimentation during adolescence is associated with increased risk of drug addiction relative to any other age group. To further understand the neurobiology underlying such liability, we investigate how early adolescent cocaine experience impacts medial prefrontal cortex (mPFC) network function in adulthood. ⋯ Our data indicate that repeated cocaine exposure during early adolescence can elicit a state of mPFC disinhibition resulting from a functional impairment of the local prefrontal GABAergic network that endures through adulthood. A lack of acquisition of prefrontal GABAergic function during adolescence could trigger long-term deficits in the mPFC that may increase the susceptibility for the onset of substance abuse and related psychiatric disorders.
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Biological psychiatry · Oct 2013
Kappa opioid receptor-mediated dysregulation of gamma-aminobutyric acidergic transmission in the central amygdala in cocaine addiction.
Studies have demonstrated an enhanced dynorphin/kappa-opioid receptor (KOR) system following repeated cocaine exposure, but few reports have focused on neuroadaptations within the central amygdala (CeA). ⋯ Together these data demonstrate that CeA dynorphin/KOR systems are dysregulated following excessive cocaine exposure and suggest KOR antagonism as a viable therapeutic strategy for cocaine addiction.
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Biological psychiatry · Aug 2013
Randomized Controlled TrialA randomized trial of a low-trapping nonselective N-methyl-D-aspartate channel blocker in major depression.
The high-affinity N-methyl-D-aspartate (NMDA) antagonist ketamine exerts rapid antidepressant effects but has psychotomimetic properties. AZD6765 is a low-trapping NMDA channel blocker with low rates of associated psychotomimetic effects. This study investigated whether AZD6765 could produce rapid antidepressant effects in subjects with treatment-resistant major depressive disorder (MDD). ⋯ In patients with treatment-resistant MDD, a single intravenous dose of the low-trapping NMDA channel blocker AZD6765 was associated with rapid but short-lived antidepressant effects; no psychotomimetic effects were observed.
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Biological psychiatry · Jul 2013
Structural changes in hippocampal subfields in major depressive disorder: a high-field magnetic resonance imaging study.
Magnetic resonance imaging (MRI) has shown lower hippocampal volume in major depressive disorder (MDD). Preclinical and postmortem studies show that chronic stress and MDD may affect hippocampal subfields differently, but MRI spatial resolution has previously been insufficient to measure subfield volumes. ⋯ Hippocampal volumes in unmedicated MDD showed evidence of localization to specific subfields and subregions, findings that appear, on the surface, consistent with preclinical evidence for localized mechanisms of hippocampal neuroplasticity. Strengths include in vivo measurement of entire hippocampal subfields and separation between unmedicated and medicated MDD. Limitations include power to control for multiple comparisons and that MRI landmarks approximate the subfields defined by cellular microstructure.