ArticlePharmacology, biochemistry, and behavior2013
Avoidance disruptive effect of clozapine and olanzapine is potentiated by increasing the test trials: further test of the motivational salience hypothesis.
Article in Pharmacology, biochemistry, and behavior, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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5 citing papers in PubMed, 12 citations in OpenAlex.
- Continuous oral olanzapine or clozapine treatment initiated in adolescence has differential short- and long-term impacts on antipsychotic sensitivity than those initiated in adulthood.European journal of pharmacology · 2024Article
- Effects of repeated quetiapine treatment on conditioned avoidance responding in rats.European journal of pharmacology · 2015Article
- Repeated administration of aripiprazole produces a sensitization effect in the suppression of avoidance responding and phencyclidine-induced hyperlocomotion and increases D2 receptor-mediated behavioral function.Journal of psychopharmacology (Oxford, England) · 2015Article
- Repeated asenapine treatment produces a sensitization effect in two preclinical tests of antipsychotic activity.Neuropharmacology · 2013Article
- Time-dependence of risperidone and asenapine sensitization and associated D2 receptor mechanism.Behavioural brain research · 2013Article
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Authors and funding
3 authors at 3 institutions in 2 countries.
Funding
Abstract
Antipsychotic drugs suppress animals' ability to avoid an aversive stimulus in the conditioned avoidance response model (CAR). This behavioral effect is thought to reflect antipsychotic activity and is suggested to be mediated by a drug's action in attenuating the motivational salience of a conditioned stimulus (CS). In the present study, we tested whether atypical antipsychotic drugs clozapine and olanzapine act through this behavioral mechanism by manipulating the number of avoidance test trials. We reasoned that more CS trials in the presence of clozapine or olanzapine would afford the drug more opportunities to decrease the motivational salience of the CS, thus avoidance decline would be greater with the increase of CS trials in each test session. In two separate experiments, adult male Sprague-Dawley rats were tested under clozapine (5.0mg/kg, sc), olanzapine (0.5mg/kg, sc) or vehicle (sterile water) for 6 consecutive days in three CS trial conditions (i.e. 3, 10, and 40 CS trials per session). Two days later, all rats were tested under the same 40-trial session after receiving clozapine (5.0mg/kg, sc) or olanzapine (0.5mg/kg, sc). Results show that repeated clozapine and olanzapine treatment persistently decreased avoidance response, and this effect was potentiated by the increase of number of CS trials in the test sessions, as the clozapine-treated or olanzapine-treated rats tested under the 40-trial or 10-trial condition had significantly lower avoidance and faster decline across-sessions than those tested under the 3-trial condition. This potentiated effect was not only seen in the total avoidance percentage, but also observed in the within-session decline pattern in the last three drug test sessions and in the final 40-trial test session. These findings suggest that the clinical efficacy of a drug can be enhanced by increasing the exposure of symptoms in the presence of the drug.
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