The insular cortex is intergration cortex of viscerosensory and visceromotor, which has projections with many encephalic regions. Insular lobe may has relation with cue memory of drug dependence due to its function of integrating and storing delighted memory from soma and viscera stimulated by drug use.The mechanism of this cue memory may completely or partly depend on function of PKMzeta, which induces and maintains LTP by increasing the number of AMPA receptor in post synapse.While PKMzeta pseudosubstrate zeta inhibitory peptide(ZIP) can reverse PKMzeta mediated LTP thus disrupt or even erase the memory depending on PKMzeta through endocytosis of AMPA receptors which decreasing the receptor’s number in post synapse. Rhesus macaques are commonly used nonhuman primate experimental animals which have more phylogenic similarity with Homo sapien than rodents especially in advanced prefrontal lobe development and cognitive ability. Morphine induced conditioned place preference(CPP) model can be established in rhesus macaques. The drug associated memory can be assessed by this preference model. We injected ZIP to insular lobe on morphine induced CPP macaques, and reduced the preference significantly. PKMzeta in insular lobe was reported to associate with conditioned taste aversion(CTA) memomry, we observed none significant result of ZIP injection to insular in macaques. Working memory (there are projections between insular and prefrontal lobe), plasma cortisone level(the relationship between anxiety and addiction) and cibation behavior (insular lobe integrates olfactory and gustatory messages) were also observed. We found plasma cortisone level decrease after surgery and the response mode to stress changed after morphine.
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