title: Effect of environmental cues on the behavioral efficacy of haloperidol, olanzapine, and clozapine in rats.
abstract: 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 (0.05 mg/kg, subcutaneously) and olanzapine (2.0 mg/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 (10.0 mg/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 (5.0 mg/kg, subcutaneously) or olanzapine (1.0 mg/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 (0.03 mg/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.
authors.affiliation: aDepartment of Neurology, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China bDepartment of Psychology, University of Nebraska-Lincoln, Lincoln, Nebraska, USA.
authors.forename: Tao
authors.initials: T
authors.lastname: Sun
authors.forename: Xinfeng
authors.initials: X
authors.lastname: Liu
authors.forename: Ming
authors.initials: M
authors.lastname: Li
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage*; D001569:Benzodiazepines / Q000008:administration & dosage*; D003024:Clozapine / Q000008:administration & dosage*; D003463:Cues; D004361:Drug Tolerance; D004777:Environment; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006220:Haloperidol / Q000008:administration & dosage*; D006799:Housing, Animal; D006948:Hyperkinesis / Q000139:chemically induced / Q000188:drug therapy*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D000077152:Olanzapine; D010622:Phencyclidine / Q000494:pharmacology; D011897:Random Allocation; D017207:Rats, Sprague-Dawley
chemical_list: D014150:Antipsychotic Agents; D018691:Excitatory Amino Acid Antagonists; D001569:Benzodiazepines; D010622:Phencyclidine; D003024:Clozapine; D006220:Haloperidol; D000077152:Olanzapine