Effect Of Chronic Morphine On Fear Extinction In Rats

Object Fear extinction deficit may induce anxiety disorders; on the other hand, epidemiology figure shows the occurrence of anxiety disorders among opiate abusers is much higher than controls with the mechanism unclear. Our research is to investigate the effect of chronic morphine on fear extinction, and further our understanding of mechanism underlying anxiety disorders among opiate abusers.Methods Rats were administrated morphine hydrochloride (iv, increasing doses) twice per day for continuous ten days to develop opiate dependence. 28 hr and 7 days after the last injection, the somatic signs of spontaneous opiate withdrawal were observed. Rats received a cued or contextual fear conditioning session 7 days after the last morphine or saline injection. During subsequent four days, rats received four cued or contextual extinction sessions (one session per day). Percent freezing was assessed during all phases of training. The unspecific effects of chronic morphine refer to the change of nociceptive response and freezing behavior caused by tone or context. The hot water tail-flick latency and locomotor activity caused by footshock were used to assess nociceptive response.Results 28 hr after the last injection, the morphine group showed significant signs of spontaneous opiate withdrawal compared with saline group, but the two groups showed no difference 7 days after the last injection. In the cued fear conditioning and extinction experiment, chronic morphine did not affect the acquisition of cued fear response or the initial encoding of extinction memory within each session, but produced an impairment in the between-session extinction. However, the same morphine treatment schedule did not affect the acquisition or extinction of contextual conditioned fear response. The two groups showed the same level of hot water tail-flick latency and locomotor activity caused by footshock and also the same level of freezing caused by the tone or context itself.Conclusion 1. The morphine treatment schedule successfully induces opiate dependence. 2. Chronic morphine selectively impaired the long-term cued fear extinction, leaving the acquisition and short-term extinction of cued fear response unaffected. And this impairment was not due to the unspecific effects of morphine administration. 3. Chronic morphine had no effect on contextual fear extinction. 4. This deficit in fear extinction may be one of those critical components that contribute to the high prevalence of anxiety disorders in opiate addicts, making it a possible animal model for these disorders.