Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
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Neuropsychopharmacology · Nov 2003
Randomized Controlled Trial Comparative Study Clinical TrialSubdissociative dose ketamine produces a deficit in manipulation but not maintenance of the contents of working memory.
We investigated the effects of subdissociative dose ketamine on executive processes during a working memory task. A total of 11 healthy volunteers participated in a double-blind, placebo-controlled, randomized, within-subjects study. They attended on three occasions, receiving intravenous infusions of placebo, a lower ketamine dose, and a higher ketamine dose. ⋯ Impairments were seen only at the higher dose of ketamine and restricted to a subgroup of the verbal working memory tasks: While visuo-spatial working memory showed no evidence of impairment, and while simple maintenance processes during verbal working memory were also unimpaired, higher dose ketamine produced a significant impairment in the manipulation of information within working memory. This process-specific effect of ketamine was reflected in a drug-by-task interaction. The specificity of this ketamine effect suggests that the earliest effect of NMDA receptor blockade is in higher order control of executive function rather than in more basic maintenance processes.
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Neuropsychopharmacology · Oct 2003
Randomized Controlled Trial Comparative Study Clinical TrialSafety and feasibility of magnetic seizure therapy (MST) in major depression: randomized within-subject comparison with electroconvulsive therapy.
Magnetic seizure therapy (MST) is a novel means of performing convulsive therapy using rapidly alternating strong magnetic fields. MST offers greater control of intracerebral current intensity than is possible with electroconvulsive therapy (ECT). These features may result in a superior cognitive side effect profile for MST, while possibly retaining the efficacy of ECT. ⋯ MST was also superior to ECT on measures of attention, retrograde amnesia, and category fluency. Magnetic seizure induction in patients with depression is feasible, and appears to have a superior acute side effect profile than ECT. Future research will be needed to establish whether MST has antidepressant efficacy.
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Neuropsychopharmacology · Jul 2003
Withdrawal from chronic amphetamine induces depressive-like behavioral effects in rodents.
Amphetamine withdrawal and major depression share many behavioral commonalities in humans. Therefore, the examination of the behavioral effects of amphetamine withdrawal in rodents may provide insights into the neurobiological mechanisms underlying both disorders and aid in the development of animal models of depression that are sensitive to antidepressant agents. ⋯ Withdrawal from chronic amphetamine administration results in behavioral changes that may be analogous to some aspects of depression in humans, such as reward deficits (i.e., elevations in brain reward thresholds) and behaviors opposite to those seen after treatment with antidepressant drugs, such as decreased immobility in the forced swim test and the tail suspension test.
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Neuropsychopharmacology · Jun 2003
The muscarinic M1/M4 receptor agonist xanomeline exhibits antipsychotic-like activity in Cebus apella monkeys.
Xanomeline is a muscarinic M(1)/M(4) preferring receptor agonist with little or no affinity for dopamine receptors. The compound reduces psychotic-like symptoms in patients with Alzheimer's disease and exhibits an antipsychotic-like profile in rodents without inducing extrapyramidal side effects (EPS) at therapeutically relevant doses. In the present study, we examined whether the xanomeline-induced functional dopamine antagonism found in rodent studies could also be observed in nonhuman primates. ⋯ However, when xanomeline was tested at 4 mg/kg, moderate dystonia was seen in two out of three monkeys. It is concluded that xanomeline inhibits D-amphetamine- and (-)-apomorphine-induced behavior in Cebus apella monkeys at doses that do not cause EPS. These data further substantiate that muscarinic receptor agonists may be useful in the pharmacological treatment of psychosis.
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Neuropsychopharmacology · May 2003
Comparative StudyDownregulation of neuronal cdk5/p35 in opioid addicts and opiate-treated rats: relation to neurofilament phosphorylation.
Neuronal cyclin-dependent kinase-5 (Cdk5) and its neuron-specific activator p35 play a major role in regulating the cytoskeleton dynamics. Since opioid addiction was associated with hyperphosphorylation of neurofilament (NF) in postmortem human brains, this study was undertaken to assess the status of the cdk5/p35 complex and its relation with NF-H phosphorylation in brains of chronic opioid abusers. Decreased immunodensities of cdk5 (18%) and p35 (26-44%) were found in the prefrontal cortex of opioid addicts compared with matched controls. ⋯ In these brains, phosphorylated NF-H significantly correlated with p35 (r=0.58) but not with cdk5 (r=0.03). The results suggest that opiate addiction is associated with downregulation of cdk5/p35 levels in the brain. This downregulation and the aberrant hyperphosphorylation of NF-H proteins might have important consequences in the development of neural plasticity associated with opiate addiction in humans.