The hippocampus is a brain region associated with learning and memory. Accumulating evidence demonstrates that it also plays a role in opioid dependence. Several studies have shown that chronic exposure to morphine or heroin leads to the impairment of hippocampal LTP and induces cognitive deficits, as shown by poor performances on memory task of heroin abusers or chronic opiate treated rodents. However, the mechanisms underlying these effects of opiates are poorly understood.

Shanghai Institute of Materia Medica and Kunming Institute of Zoology collaboratively identified a potential mechanism by which chronic exposure to opiates lead to impairment of Hippocampal long-term potentiation and spatial memory. This work was recently published on the Journal of Neuroscience. This work was mainly carried out by Dr. Gang Lu and Dr. Qing-xin Zhou from research teams of Prof.Jing-gen Liu and Prof. Lin Xu., respectively.

Brain cognitive deficit is one of the side effects of opiates. Increasing discoveries indicate that cognitive deficits possibly relate to addicts’ compulsive drug-taking and relapse after withdrawal. However, the mechanisms underlying these effects of opiates are poorly understood. This work has found that chronic morphine treatment in mice leads to a significant increase of hippocampal extracellular adenosine concentrations, which contributes to the inhibition of the hippocampal CA1 LTP and impairment of spatial memory retrieval via activation of Adenosine A1 Receptors.They further found that adenosine accumulation is attributable to the attenuation of adenosine uptake due to the impairment of the equilibrative nucleoside transporter (ENT2) function and down-regulation of PKC-α/β activity.This study may help to explain the mechanism of opiates dependence.

This program is supported by National Science Fund for Distinguished Young Scholars, National Program on Key Basic Research Project (973 Program) and Key Program of the Chinese Academy of Sciences