RT Journal Article
SR Electronic
T1 Stress Enables Synaptic Depression in CA1 Synapses by Acute and Chronic Morphine: Possible Mechanisms for Corticosterone on Opiate Addiction
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 2412
OP 2420
DO 10.1523/JNEUROSCI.5544-03.2004
VO 24
IS 10
A1 Ya Yang
A1 Xigeng Zheng
A1 Yongfu Wang
A1 Jun Cao
A1 Zhifang Dong
A1 Jingxia Cai
A1 Nan Sui
A1 Lin Xu
YR 2004
UL http://www.jneurosci.org/content/24/10/2412.abstract
AB 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 (∼20%) to synaptic depression (∼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.