Time-dependent sensitization of antipsychotic effect in adolescent male and female rats

Ding, Xin; Li, Xiaonan; Shu, Qing; Wu, Ruiyong; Hu, Gang; Li, Ming

doi:10.1016/j.bbr.2017.04.013

Cited by 3 publications

(1 citation statement)

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“…We termed this increased drug sensitivity due to past drug use ‘antipsychotic sensitization’, which is also context dependent (Li, 2016; Li et al, 2009a; Sparkman and Li, 2012; Zhang and Li, 2012). One interesting finding is that there is often a reciprocal transfer between different drug-induced sensitizations (between haloperidol and olanzapine; between risperidone and olanzapine; and between asenapine and olanzapine) (Li et al, 2007; Mead and Li, 2010; Qin et al, 2013; Zhang and Li, 2012), and it can be demonstrated in adolescence and detected in adulthood (Ding et al, 2017; Qiao et al, 2013, 2014a, 2014b; Shu et al, 2014b). The present study found some similar properties in RA.…”

Section: Discussionmentioning

confidence: 99%

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

Gao

2018

J Psychopharmacol

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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.

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