Acute withdrawal from repeated cocaine treatment enhances latent inhibition of a conditioned fear response

Psychostimulant-induced locomotor sensitization and disrupted latent inhibi tion (LI) of a classically conditioned association are two paradigms that h ave been widely studied as animal behavioural models of psychosis, In this study we assessed the effects of withdrawal from the repeated intermittent administration of cocaine on LI of a conditioned fear response. Animals whi ch were either preexposed (PE) to a tone conditioned stimulus (CS) or naive to the tone (i.e. non-preexposed: NPE) subsequently experienced 10 pairing s of the tone CS with footshock, Afterwards, both groups received five dail y injections of cocaine (20 mg/kg, i.p.) or saline. After 3 days of withdra wal from drug treatment, animals were tested for conditioned freezing to th e context of the footshock chamber, and 1 day later, for conditioned freezi ng to the tone CS, Cocaine-sensitized animals exhibited markedly enhanced L I compared to saline-treated animals, due to the fact that NPE-cocaine anim als spent more time freezing during the tone CS than NPE-saline animals, wh ereas PE-cocaine animals showed a tendency toward reduced freezing compared to the saline groups. While these results suggest the presence of increase d anxiety in cocaine-withdrawn NPE animals, the absence of this effect in c ocaine-withdrawn PE rats indicates that cocaine withdrawal also influences the retrieval of previously learned information. (C) 2001 Lippincott Willia ms & Wilkins.