BACKGROUND AND PURPOSE:

The endocannabinoid (eCB) system is involved in pathways that regulate drug addiction, and eCB-mediated synaptic plasticity has been linked with addictive behaviors. Here, we investigated molecular mechanisms underlying changes in eCB-dependent synaptic plasticity in nucleus accumbens core (NAcc) following short-term withdrawal from repeated morphine treatment.

EXPERIMENTAL APPROACH:

Conditioned place preference (CPP) was used to evaluate the rewarding effects of morphine in rats. Evoked inhibitory postsynaptic currents (eIPSCs) of medium spiny neurons (MSNs) in NAcc were measured using whole-cell patch-clamp recordings. To investigate the effect of short-term morphine withdrawal on the eCB system, changes in depolarization-induced suppression of inhibition (DSI) in NAcc were subsequently assessed. To identify the potential modulation mechanism of short-term morphine withdrawal on the eCB system, the expression of diacylglycerol lipase alpha (DGL-α) and monoacylglycerol lipase (MGL) was detected by western blotting analysis.

KEY RESULTS:

Stable CPP was induced after repeated morphine administration for 7 days. Compared to the saline group, the level of DSI in NAcc was significantly increased in rats after short-term morphine withdrawal. Furthermore, this increase in DSI coincided with a significant increase in the expression of DGL-α.

CONCLUSIONS AND IMPLICATIONS:

Our study demonstrated that short-term morphine withdrawal potentiates eCB modulation of inhibitory synaptic transmission in NAcc. We also found that DGL-α expression was elevated after short-term morphine withdrawal, suggesting that the eCB 2-arachidonyl-glycerol (2-AG) but not anandamide (AEA) might mediate the increase in DSI magnitude. These provide useful insights into the mechanisms underlying eCB-mediated plasticity in NAcc during drug addiction.
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