Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
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Although placebos have long been considered a nuisance in clinical research, today they represent an active and productive field of research and, because of the involvement of many mechanisms, the study of the placebo effect can actually be viewed as a melting pot of concepts and ideas for neuroscience. Indeed, there exists not a single but many placebo effects, with different mechanisms and in different systems, medical conditions, and therapeutic interventions. For example, brain mechanisms of expectation, anxiety, and reward are all involved, as well as a variety of learning phenomena, such as Pavlovian conditioning, cognitive, and social learning. ⋯ First, as the placebo effect is basically a psychosocial context effect, these data indicate that different social stimuli, such as words and rituals of the therapeutic act, may change the chemistry and circuitry of the patient's brain. Second, the mechanisms that are activated by placebos are the same as those activated by drugs, which suggests a cognitive/affective interference with drug action. Third, if prefrontal functioning is impaired, placebo responses are reduced or totally lacking, as occurs in dementia of the Alzheimer's type.
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Neuropsychopharmacology · Jan 2011
NMDA receptor hypofunction phase couples independent γ-oscillations in the rat visual cortex.
Hallucinations, a hallmark of psychosis, can be induced by the psychotomimetic N-methyl-D-aspartic acid (NMDA) receptor antagonists, ketamine and phencyclidine (PCP), and are associated with hypersynchronization in the γ-frequency band, but it is unknown how reduced interneuron activation associated with NMDA receptor hypofunction can cause hypersynchronization or distorted perception. Low-frequency γ-oscillations (LFγ) and high-frequency γ-oscillations (HFγ) serve different aspects of perception. In this study, we test whether ketamine and PCP affect the interactions between HFγ and LFγ in the rat visual cortex in vitro. ⋯ Selective NMDA receptor antagonism, selective NR2B subunit-containing receptor antagonism, and reduced D-serine levels caused a similar selective deceleration of HFγ, whereas increasing NMDA receptor activation through exogenous NMDA, D-serine, or mGluR group 1 agonism selectively accelerated HFγ. The NMDA receptor hypofunction-induced phase coupling of the normally independent γ-generating networks is likely to cause abnormal cross-layer interactions, which may distort perceptions due to aberrant matching of top-down information with bottom-up information. If decelerated HFγ and subsequent cross-layer synchronization also underlie pathological psychosis, acceleration of HFγ could be the target for improved antipsychotic therapy.
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Neuropsychopharmacology · Jan 2011
Randomized Controlled TrialThe subjective, reinforcing, and analgesic effects of oxycodone in patients with chronic, non-malignant pain who are maintained on sublingual buprenorphine/naloxone.
Some sources suggest that significant misuse of opioid drugs exists among patients with chronic pain. However, the risk factors and motivation behind their abuse may differ from those of other opioid abusers. This study sought to examine the abuse liability of oxycodone among patients with chronic, non-malignant pain who met the DSM-IV criteria for opioid abuse. ⋯ Furthermore, unlike our findings in recreational opioid users and more similar to effects in non-drug-abusing individuals, oxycodone failed to serve as a reinforcer. As for the maintenance drug, Bup/Nx produced a dose-related reduction in some of the effects of acutely administered oxycodone. These data suggest that sublingual Bup/Nx has the potential as an analgesic medication and further research should investigate its use in treating patients with chronic pain who abuse opioids.
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Neuropsychopharmacology · Jan 2011
Comparative StudyDissociable roles of prelimbic and infralimbic cortices, ventral hippocampus, and basolateral amygdala in the expression and extinction of conditioned fear.
Current models of conditioned fear expression and extinction involve the basolateral amygdala (BLA), ventral medial prefrontal cortex (vmPFC), and the hippocampus (HPC). There is some disagreement with respect to the specific roles of these structures, perhaps due to subregional differences within each area. For example, growing evidence suggests that infralimbic (IL) and prelimbic (PL) subregions of vmPFC have opposite influences on fear expression. ⋯ Inactivation of the BLA or vHPC impaired both fear expression and extinction memory. Post-extinction inactivations had no effect in any structure. We suggest a model in which amygdala-dependent fear expression is modulated by inputs from PL and vHPC, whereas extinction memory requires extinction-induced plasticity in IL, BLA, and/or vHPC.
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Neuropsychopharmacology · Jan 2011
Regulation of hippocampal cannabinoid CB1 receptor actions by adenosine A1 receptors and chronic caffeine administration: implications for the effects of Δ9-tetrahydrocannabinol on spatial memory.
The cannabinoid CB(1) receptor-mediated modulation of γ-aminobutyric acid (GABA) release from inhibitory interneurons is important for the integrity of hippocampal-dependent spatial memory. Although adenosine A(1) receptors have a central role in fine-tuning excitatory transmission in the hippocampus, A(1) receptors localized in GABAergic cells do not directly influence GABA release. CB(1) and A(1) receptors are the main targets for the effects of two of the most heavily consumed psychoactive substances worldwide: Δ(9)-tetrahydrocannabinol (THC, a CB(1) receptor agonist) and caffeine (an adenosine receptor antagonist). ⋯ Chronic administration of caffeine in mice (intraperitoneally, 3 mg/kg/day, for 15 days, >12 h before trials) led to an A(1)-mediated enhancement of the CB(1)-dependent acute disruptive effects of THC on a short-term spatial memory task, despite inducing a reduction in cortical and hippocampal CB(1) receptor number and an attenuation of CB(1) coupling with G protein. A(1) receptor levels were increased following chronic caffeine administration. This study shows that A(1) receptors exert a negative modulatory effect on CB(1)-mediated inhibition of GABA and glutamate release, and provides the first evidence of chronic caffeine-induced alterations on the cannabinoid system in the cortex and hippocampus, with functional implications in spatial memory.