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

Subiculum receives output of hippocampal CA1 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 the subicular-NAc pathway. Here, we recorded the field excitatory postsynaptic potential (EPSP) within the shell of NAc by stimulating ventral subiculum in anesthetized adult rats. We found that high frequency stimulation (HFS, 200 Hz) induced long-term potentiation (LTP) but low frequency stimulation (LFS, 1 Hz) failed to induce long-term depression (LTD) in control animals. However, behavioral stress enabled LFS to induce a reliable LTD (sLTD) that was dependent on the glucocorticoid receptors. Both LTP and sLTD were prevented by the N-methyl-d-aspartate receptor antagonist AP-5. After repeated morphine treatment for 12 days, acute withdrawal (12 h) impaired LTP but had no effect on sLTD; prolonged withdrawal (4 days) restored the LTP but impaired the sLTD. Remarkably, basal synaptic efficacy reflected by baseline EPSP amplitude was potentiated in acute withdrawal but was depressed in prolonged withdrawal. Thus, acute and prolonged opiate withdrawal may cause endogenous LTP and LTD in the subicular-NAc pathway that occludes the subsequent induction of synaptic plasticity, demonstrating adaptive changes of the NAc functions during opiate withdrawal.