Reinforcement attenuation as a behavioral technique to suppress conditioned avoidance response in rats: A comparative study with olanzapine

Background: Antipsychotic treatment is effective in the treatment of psychosis, although it also brings with it some unwanted side effects and is associated with low compliance. Finding a non-pharmacological alternative for antipsychotic treatment is highly desirable. Aims: This preclinical study examined the ‘antipsychotic’ efficacy of such a behavioral technique using a conditioned avoidance response model. This technique, termed reinforcement attenuation (RA), is to administer a brief footshock (0.1–2.0 s, 0.8 mA) at the end of each trial regardless of whether a well-trained rat makes an avoidance response or not. Results: RA achieved the same avoidance suppressing effect as olanzapine (an atypical antipsychotic drug), including both acute suppression and sensitized suppression of avoidance response in well-trained Sprague–Dawley adult male rats. Interestingly, the RA-induced sensitization (an enhanced disruption of avoidance responding) enhanced subsequent olanzapine sensitivity, whereas the olanzapine (1.0 mg/kg)-induced sensitization had little impact on later RA treatment. When RA and olanzapine (0.5 mg/kg, subcutaneously) were used together, the RA-induced sensitization was still detectable in the RA challenge test, although its magnitude was reduced by olanzapine. Finally, we showed that the RA-induced sensitization in avoidance suppression persisted from adolescence into adulthood, long after such a treatment was terminated. Conclusions: These findings demonstrate that the RA is functionally equivalent (if not superior) to antipsychotic treatment in the avoidance suppression effect (both acute and sensitization effects) in both adolescent and adult animals. Behavioral therapies that specifically target the reinforcer of psychotic thoughts might be a viable strategy for the treatment of psychosis.