Chronic Morphine Selectively Impairs Cued Fear Extinction in Rats: Implications for Anxiety Disorders Associated with Opiate Use

Previous studies have shown that opioid transmission plays an important role in learning and memory. However, little is known about the course of opiate-associated learning and memory deficits after cessation of chronic opiate use in a behavioral animal model. In the present study, we examined the effects of chronic morphine on fear extinction, an important preclinical model for behavior therapy of human anxiety disorders. Rats were administrated subcutaneously morphine hydrochloride or saline twice per day for continuous 10 days. Rats received a cued or contextual fear conditioning session 7 days after the last morphine injection. During subsequent days, rats received four cued or contextual extinction sessions (one session per day). Percent freezing was assessed during all phases of training. 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 fear response. These results suggest that the effects of chronic morphine on memory for fear extinction are complex. Chronic morphine selectively impairs extinction of cued fear response. This deficit in fear extinction may be one of those critical components that contribute to the high prevalence of anxiety disorders in opiate addicts.