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Opioid addiction is associated with long-term adaptive changes in the brain that involves protein expression.The carboxyl-terminal of the μ opioid receptor (MOR-C) is important for receptor signal transduction after opioid agonist treatment.However, the proteins that interact with MOR-C after chronic morphine exposure remain unknown.In the present study, a brain cDNA library from chronic morphine-dependent rats was constructed using the SMART (Switching Mechanism At 5 end of RNA Transcript) technique.The cDNA library consisted of 3.05 × 106 recombinants.Bacterial two-hybrid screening identified 21 clones that interacted with rat MORC.Homology searches of these clones against the GenBank database determined that 19 clones encoded known proteins and two clones encoded novel proteins.