NPY alterations induced by chronic morphine exposure affect the maintenance and reinstatement of morphine conditioned place preference.

Opioid addiction is a brain disease that severely harms society and personal health. Although the tremendous numbers of patients worldwide and emerged negative events, effective treatments for opioid addiction are still lacking. Neuropeptide Y (NPY) is one of the main orexigenic peptides that play vital roles in food intake and energy metabolism. However, increasing evidence indicates that NPY may have great potential in mediating reward effects and drug dependence. In the present study, we assessed the expression changes of NPY in the nucleus accumbens at different timepoints following morphine conditioned place preference (CPP) and investigated the functional importance of potential NPY changes. Our results showed that NPY expression significantly decreased in the nucleus accumbens shell (AcbSh) immediately after chronic morphine exposure. Subsequently, it increased rapidly at first and then gradually returned to normal levels. Further data indicated that these NPY changes were involved in morphine reward memory, demonstrated by a reduction in the extinction period after blocking of the Y5 receptor by L-152,804 in the AcbSh and a prolonged duration of the extinction period following the application of NPY. More importantly, the additional results revealed that L-152,804 also remarkably suppressed the reinstatement of morphine CPP. Together, our results indicate that a complicated plasticity of the NPY pathway in AcbSh occurs following morphine CPP, and this plasticity plays an important role in modulating morphine reward memory. These findings may enhance our understanding of the role of the NPY system in opioid addiction and indicate a promising target for opioid addiction treatment.