Avoidance-suppressing effect of antipsychotic drugs is progressively potentiated after repeated administration

An interoceptive drug state mechanism

A. Mead, Ming Li

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Antipsychotic drugs selectively suppress conditioned avoidance response. Using a two-way active avoidance response paradigm, we examined the role of drug-induced interoceptive state in the mediation of avoidance-suppressive effect. In Experiment 1, we found that rats intermittently treated with olanzapine (OLZ) (1.0 mg/kg, s.c.) or haloperidol (0.03 mg/kg, s.c.) on the 1st day of a 3-day cycle for seven cycles exhibited a progressive across-session decline in avoidance responding, despite the fact that they exhibited a comparable high level of avoidance responding on the 3rd day of each cycle during the drug-free retraining session. In Experiments 2 and 3, rats that were previously treated with OLZ (0.5-2.0 mg/kg, s.c.) or risperidone (0.2-1.0 mg/kg) during the acquisition phase of avoidance conditioning exhibited significantly fewer avoidance responses when they were retested 3 weeks later to the same drug in comparison to rats that were previously treated with nonantipsychotic drugs (chlordiazepoxide, 10 mg/kg, citalopram 10 mg/kg, or sterile water). Overall, these findings indicate a drug memory-like mechanism that maintains the avoidance-suppressing effect of antipsychotics over time. This mechanism is likely driven by the interoceptive state caused by the antipsychotics, which may also be an important behavioral mechanism mediating the clinical effects of antipsychotic treatments.

Original languageEnglish (US)
Pages (from-to)1045-1053
Number of pages9
JournalJournal of Psychopharmacology
Volume24
Issue number7
DOIs
StatePublished - Jul 1 2010

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Antipsychotic Agents
olanzapine
Pharmaceutical Preparations
Chlordiazepoxide
Citalopram
Risperidone
Haloperidol
Water

Keywords

  • Conditioned avoidance response
  • Drug memory
  • Haloperidol
  • Interoceptive drug state
  • Olanzapine
  • Rat
  • Risperidone

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health
  • Pharmacology (medical)

Cite this

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abstract = "Antipsychotic drugs selectively suppress conditioned avoidance response. Using a two-way active avoidance response paradigm, we examined the role of drug-induced interoceptive state in the mediation of avoidance-suppressive effect. In Experiment 1, we found that rats intermittently treated with olanzapine (OLZ) (1.0 mg/kg, s.c.) or haloperidol (0.03 mg/kg, s.c.) on the 1st day of a 3-day cycle for seven cycles exhibited a progressive across-session decline in avoidance responding, despite the fact that they exhibited a comparable high level of avoidance responding on the 3rd day of each cycle during the drug-free retraining session. In Experiments 2 and 3, rats that were previously treated with OLZ (0.5-2.0 mg/kg, s.c.) or risperidone (0.2-1.0 mg/kg) during the acquisition phase of avoidance conditioning exhibited significantly fewer avoidance responses when they were retested 3 weeks later to the same drug in comparison to rats that were previously treated with nonantipsychotic drugs (chlordiazepoxide, 10 mg/kg, citalopram 10 mg/kg, or sterile water). Overall, these findings indicate a drug memory-like mechanism that maintains the avoidance-suppressing effect of antipsychotics over time. This mechanism is likely driven by the interoceptive state caused by the antipsychotics, which may also be an important behavioral mechanism mediating the clinical effects of antipsychotic treatments.",
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