| 其他摘要 | Synaptic plasticity is the ability of the connection, or synapse, between two neurons to change in strength. It is believed to be the mechanism underlying certain types of learning and memory, and two forms (LTP and LTD) of it are widely studied in various brain regions to understand the properties of learning and memory. Stress is an individual physical and mental reaction to environmental demands or pressures. It is always accompanied with elevating the concentration of glucocorticoids, which normally maintain at a level that will make pepole to be alert, to ready for escape or something. Furthermore, stress or elevated glucocorticoids will affect the learning and memory. Addiction can be best defined as the loss of control over drug use, or the compulsive seeking and taking of drugs despite adverse consequences. By some views, addiction is some kind of memory, but it is more powerful in utilizing the neural circuit, the plasticity they affect is much more intense than that of the physilogical stimuli does. The cardinal features of drug addiction are the compulsive seeking and taking of drugs. Once formed, an addiction can be a life-long condition in which individuals show intense drug craving and increased risk for relapse after years and even decades of abstinence. After several decades of studying on addiction and memory, evidence showes that addiction and memory share many neural circuit and converge in some of them, and even share the same mechanism. Therefore, we can apply the methods usually used for studying learning and memory to study addiction. On the contrary, addiction is also an ideal model used to study learning and memory. Stress can influence synaptic plasticity and learning and memory, and drug withdrawal per se can evoke stress. Thus, we may provide potential therapeutic strategies to reduce drug craving and prevent relapses, through studying the effects of drug withdrawal and stress on synaptic plasticity and learning and memory. In our present study, we use electrophysiological, behavioral and biochemical methods to examine the effects of morphine withdrawal and withdrawal-evoked stress on synaptic plasticity and learning and memory. The electrophysiological results showed that: the magnitude of hippocampal CA1 LTP displayed an inverted-U curve during morphine withdrawal, and the largest magnitude occurred on 4-day withdrawal. Stress remarkedly facilitated LTP at 18-hour withdrawal, similar to the large LTP found on 4-day withdrawal. Furthermore, glucocorticoid receptor (GRs) antagonist RU38486 treatment or an extinction dose of morphine suppressed the large LTP on 4-day withdrawal, to a level similar to that found at 18-hour withdrawal. In addition, synaptic plasticity in subicular–nucleus accumbens (NAc) pathway also showed time-dependent alteration during morphine withdrawal, similar to those found in hippocapal CA1. The behavioral results showed that: morphine withdrawal reduced pain threshod and antinociceptive effects of acute morphine, in which GRs play significant roles. In addition, the formation of morphine conditioned place preference (CPP) depended on both the GRs of hippocampus and NAc. The biochemical results showed that: morphine withdrawal induced dynamic expression of GluR1 and GluR2/3 subunits of AMPA receptors and its regulatory molecule CaMKIIα in hippocampal synapses. In the present experiment, we found stress evoked by morphine withdrawal affect synaptic plasticity and learning and memory. These results may provide potential therapeutic strategies to reduce drug craving and to prevent relapses. |
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