Opiate withdrawal induces dynamic-expressions of AMPA receptors and its regulatory molecule CaMKII alpha in hippocampal synapses

Adaptive changes in brain areas following drug withdrawal are believed to contribute to drug seeking and relapse. Cocaine withdrawal alters the expression of GluR1 and GluR2/3 subunits of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) rec

EEG activities in the orbitofrontal cortex and dorsolateral prefrontal cortex during the development of morphine dependence, tolerance and withdrawal in rhesus monkeys

Investigating the activities of the prefrontal cortex (PFC) in the process of addiction is valuable for understanding the neural mechanism underlying the impairments of the PFC after drug abuse. However, limited data are obtained from primate animals and few studies analyze Electroencephalogram (EEG) in the gamma band, which plays an important role in cognitive functions. In addition, it is yet unclear whether drug abuse affects the orbitofrontal cortex (OFC) and dorsolateral PFC (DLPFC) - the two most important subregions of the PFC - in similar ways or not. The aim of this study is to address these issues. We recorded EEG in the OFC and DLPFC in three rhesus monkeys. All animals received a course of saline (NaCl 0.9%, 2 ml) injection (5 days) followed by 10 days of morphine injection (every 12 h), and then a further series of saline injection (7 days). A main finding in the present study was that morphine decreased EEG power in all frequency bands in a short period after injection in both the OFC and DLPFC in monkeys. And gamma power decreased not just in short period after morphine injection but lasted to 12 h after injection. Moreover, we found that although the changes in EEG activities in the OFC and DLPFC at 30-35 min after injection were similar, the DLPFC was more sensitive to the effect of morphine than the OFC. (c) 2005 Elsevier B.V. All rights reserved.

Opioid Withdrawal for 4 Days Prevents Synaptic Depression Induced by Low Dose of Morphine or Naloxone in Rat Hippocampal CA1 Area In Vivo

The formation of memory is believed to depend on experience- or activity-dependent synaptic plasticity, which is exquisitely sensitive to psychological stress since inescapable stress impairs long-term potentiation (LTP) but facilitates long-term depression (LTD). Our recent studies demonstrated that 4 days of opioid withdrawal enables maximal extents of both hippocampal LTP and drug-reinforced behavior; while elevated-platform stress enables these phenomena at 18 h of opioid withdrawal. Here, we examined the effects of low dose of morphine (0.5 mg kg(-1), i.p.) or the opioid receptor antagonist naloxone (1 mg kg(-1), i.p.) on synaptic efficacy in the hippocampal CA1 region of anesthetized rats. A form of synaptic depression was induced by low dose of morphine or naloxone in rats after 18 h but not 4 days of opioid withdrawal. This synaptic depression was dependent on both N-methyl-D-aspartate receptor and synaptic activity, similar to the hippocampal long-term depression induced by low frequency stimulation. Elevated-platform stress given 2 h before experiment prevented the synaptic depression at 18 h of opioid withdrawal; in contrast, the glucocorticoid receptor (GR) antagonist RU38486 treatment (20 mg kg(-1), s.c., twice per day for first 3 days of withdrawal), or a high dose of morphine reexposure (15 mg kg(-1), s.c., 12 h before experiment), enabled the synaptic depression on 4 days of opioid withdrawal. This temporal shift of synaptic depression by stress or GR blockade supplements our previous findings of potentially correlated temporal shifts of LTP induction and drug-reinforced behavior during opioid withdrawal. Our results therefore support the idea that stress experience during opioid withdrawal may modify hippocampal synaptic plasticity and play important roles in drug-associated memory. (C) 2009 Wiley-Liss, Inc.

Effects of morphine and its withdrawal on Y-maze spatial recognition memory in mice

Effects of morphine on acquisition and retrieval of memory have been proven in the avoidance paradigms. In present study, we used a two-trial recognition Y-maze to test the effects of acute morphine and morphine withdrawal on spatial recognition memory. T

Dynamic changes in orbitofrontal neuronal activity in rats during opiate administration and withdrawal

The orbitofrontal cortex is involved in the reinforcing effects of drugs of abuse. However, how the dynamic activity in OFC changes during opiate administration and withdrawal period has not been investigated. We first tested the effects of opiates and dr

Human immunodeficiency virus-1 genotypic drug resistance among volunteer blood donors in Yunnan, China

BACKGROUND: Drug resistance profiles of human immunodeficiency virus-1 (HIV-1) in treatment-naive infections have been reported in developed countries. However, little is known in developing countries, including China, especially in treatment-naive volunt

The dynamics of hippocampal sensory gating during the development of morphine dependence and withdrawal in rats

The effects of morphine on hippocampal sensory gating (N40) during the development of morphine dependence and withdrawal were investigated in the double click auditory evoked potential (EP) suppression paradigm. Rats were made dependent upon morphine hydrochloride by a series of injections (every 12h) over 6 days, followed by withdrawal after stopping morphine administration. Hippocampal gating was examined during the development of dependence and withdrawal. Moreover, the DA antagonist haloperidol was used to assess the contribution of dopamine to hippocampal gating induced by morphine. Our results showed that the morphine-treated rats exhibited significantly disrupted hippocampal gating during the development of morphine dependence and this disrupted gating was partially reversed by haloperidol pretreatment. In contrast, there was significantly enhanced hippocampal gating at the fifth and sixth days of withdrawal. The dynamics of hippocampal gating during the development of morphine dependence and withdrawal suggests the interaction between the hippocampus and opioids. (c) 2005 Elsevier Ireland Ltd. All rights reserved.

Extremely low-frequency electromagnetic field exposure during chronic morphine treatment strengthens downregulation of dopamine D2 receptors in rat dorsal hippocampus after morphine withdrawal

The aim of this study was to investigate the effect of extremely low-frequency electromagnetic field (ELF-EMF) exposure during morphine treatment on dopamine D2 receptor (D2R) density in the rat dorsal hippocampus following withdrawal. Rats were exposed t

Complete genomic sequences for hepatitis C virus subtypes 6e and 6g isolated from Chinese patients with injection drug use and HIV-1 co-infection

In one of our recent studies, two HCV genotype 6 variants were identified in patients from Hong Kong and Guangxi in southern China, with injection drug use and HIV-1 co-infection. We report the complete genomic sequences for these two variants: GX004 and

Stress enables synaptic depression in CA1 synapses by acute and chronic morphine: Possible mechanisms for corticosterone on opiate addiction

The hippocampus, being sensitive to stress and glucocorticoids, plays significant roles in certain types of learning and memory. Therefore, the hippocampus is probably involved in the increasing drug use, drug seeking, and relapse caused by stress. We have studied the effect of stress with morphine on synaptic plasticity in the CA1 region of the hippocampus in vivo and on a delayed-escape paradigm of the Morris water maze. Our results reveal that acute stress enables long-term depression (LTD) induction by low-frequency stimulation (LFS) but acute morphine causes synaptic potentiation. Remarkably, exposure to an acute stressor reverses the effect of morphine from synaptic potentiation ( similar to 20%) to synaptic depression ( similar to 40%), precluding further LTD induction by LFS. The synaptic depression caused by stress with morphine is blocked either by the glucocorticoid receptor antagonist RU38486 or by the NMDA-receptor antagonist D-APV. Chronic morphine attenuates the ability of acute morphine to cause synaptic potentiation, and stress to enable LTD induction, but not the ability of stress in tandem with morphine to cause synaptic depression. Furthermore, corticosterone with morphine during the initial phase of drug use promotes later delayed-escape behavior, as indicated by the morphine-reinforced longer latencies to escape, leading to persistent morphine-seeking after withdrawal. These results suggest that hippocampal synaptic plasticity may play a significant role in the effects of stress or glucocorticoids on opiate addiction.

Stress evoked by opiate withdrawal facilitates hippocampal LTP in vivo

Stress impairs hippocampal long-term potentiation (LTP), but it is unknown whether the stress evoked by opiate withdrawal has the same effect. Here the authors report that opiate withdrawal for 4 days does not influence basal synaptic transmission, but re

Morphine withdrawal modifies antinociceptive effects of acute morphine in rats

Repeated opioid use is known to cause tolerance of antinociceptive effects. Whether opioid abstinence modifies antinociceptive effects is unknown. Here we reported that morphine withdrawal for 18 h and 4 days after repeated morphine treatment largely redu

Opiate withdrawal modifies synaptic plasticity in subicular-nucleus accumbens pathway in vivo

Subiculum receives output of hippocampal CAI neurons and projects glutamatergic synapses onto nucleus accumbens (NAc), the subicular-NAc pathway linking memory and reward system. It is unknown whether morphine withdrawal influences synaptic plasticity in

Morphine withdrawal affects both delayed-escape behaviour in Morris water maze and hippocampal NR2A/2B expression ratio

Repeated low-dose morphine treatment facilitates delayed-escape behaviour of hippocampus-dependent Morris water maze and morphine withdrawal influences hippocampal NMDA receptor-dependent synaptic plasticity. Here, we examined whether and how morphine wit

Abnormal regional homogeneity of drug-naive obsessive-compulsive patients

To explore the possible abnormal resting-state activity in patients with obsessive-compulsive disorder (OCD), the regional homogeneity (ReHo) of 22 pairs of patients and well-matched healthy controls was calculated. Compared with controls, the patients showed higher ReHo in the left anterior cingulate cortex, but lower ReHo in the left inferior temporal gyrus. These findings supported the abnormal resting-state brain activity in drug-naive OCD patients. No significant correlations between ReHo value and four clinical characteristics were found, suggesting that abnormal ReHo might be trait-related in OCD. NeuroReport 21:786-790 (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.