Opioid dependence is a chronic relapsing disorder in the brain characterized by compulsive drug taking and the emergence of withdrawal syndrome after cessation of drug taking. Negative affection induced by drugs-withdraw is one of powerful reinforcers, which contributes so much to the relapse or sustained drug abuse. According to reports the morphine-indeuced withdrawal was correlated with the activation of the dorsal hippocampus (DH). The elevated level of Ca2+ in DH is not only a sign of its activation, but also is the central link among the intracellular signal transduction. Therefore, the regulation of calcium channel on Ca2+ transmembrane transport is the key factors of negative emotion memory induced by morphine withdrawal. L-type voltage gated calcium channels (LTCCs) can regulate the activity of some other types of calcium channels such as NMDA and RyR receptors, changes the intracellular Ca2+, thereby regulating morphine withdrawal. The present proposal based on this hypothesis, using conditioned place aversion (CPA) paradigm in rats, we will investigate whether the level of intracellular Ca2+ in hippampal CA1 was increased after the injection of naloxone in chronic morphine-dependent rats. In addition, the different effects of LTCCs subtypes Cav1.2 and Cav1.3 on the CPA induced by morphine withdrawal will also be examined. Moreover, we will test what were the downstream signal pathways of LTCCs during the acquisition of negative emotion memory induced by morphine withdrawal. The main results are as follows:

1 .The level of intracellular Ca2+ in hippampal CA1 was increased after the injection of naloxone in chronic morphine-dependent rats. And this increase was dependent on the activity of LTCCs.

2. Intra-CA1 administration of LTCCs antagionst blocked the acquisition of CPA induced by morphine withdrawal, indicating that LTCCs was involved in the acquisition of negative emotin memory in the CA1 of rats.

3. After the injection of naloxone in chronic morphine-dependent rats, the expression of Cav1.3 was obviously increased in the CAl，whereas Cavl.2 protein expresson was significantly increased in the CA1 after the acquisition of morphine CPA. These results suggested that Cavl.3 specifically regulate morphine withdrawal, Cavl.2 selectively involved in the acquisition of negative emotion memory in the CA1.

4. Cavl.2 regulated the acquisition of morphine CPA via activating the MAPK-ERIC signaling pathway in the CA1.