Effect of environmental cues on the behavioral efficacy of haloperidol, olanzapine, and clozapine in rats

Tao Sun, Xinfeng Liu, Ming Li

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


Previous studies have reported that context can powerfully modulate the inhibitory effect of an antipsychotic drug on phencyclidine (PCP)-induced hyperlocomotion (a behavioral test used to evaluate putative antipsychotic drugs). The present study investigated the experimental conditions under which environmental stimuli exert their influence through associative conditioning processes. Experiment 1 examined the extent to which previous antipsychotic treatment in the home cages affected a drug's ability to inhibit PCP-induced hyperlocomotion in novel motor activity test apparatus. Five days of repeated haloperidol (0.05mg/kg, subcutaneously) and olanzapine (2.0mg/kg, subcutaneously) treatment in the home cages still potentiated their inhibition of PCP-induced hyperlocomotion (i.e. sensitization) assessed in a new environment, whereas the clozapine (10.0mg/kg, subcutaneously) treatment enhanced the development of clozapine tolerance, indicating a lack of environmental modulation of antipsychotic efficacy. Experiment 2 assessed the impact of different numbers of antipsychotic administrations (e.g. 4, 2 or 0), in either the home environment or test environment, on a drug's ability to inhibit PCP-induced hyperlocomotion. Repeated administration of clozapine (5.0mg/kg, subcutaneously) or olanzapine (1.0mg/kg, subcutaneously) for 4 consecutive days, irrespective of where these treatments occurred, led to a similar level of inhibition of PCP-induced hyperlocomotion. However, 4-day haloperidol (0.03mg/kg, subcutaneously) treatment in the test apparatus led to significantly higher inhibition than a 4-day home-cage treatment. Thus, more exposures to the test environment under the influence of haloperidol (but not clozapine or olanzapine) caused a stronger inhibition than fewer exposures, indicating a strong environmental modulation. Collectively, these findings suggest that previous antipsychotic treatment in one environment could alter later antipsychotic-like response assessed in a different environment under certain test conditions. Therefore, whether the circumstances surrounding antipsychotic drug administration have a powerful effect on the expression of antipsychotic-like efficacy is dependent on specific experimental and drug treatment factors.

Original languageEnglish (US)
Pages (from-to)277-286
Number of pages10
JournalBehavioural pharmacology
Issue number4
StatePublished - Aug 2014


  • clozapine
  • contextual control
  • haloperidol
  • locomotor activity,olanzapine
  • phencyclidine
  • rat
  • sensitization
  • tolerance

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health


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