Long-term impacts of adolescent risperidone treatment on behavioral responsiveness to olanzapine and clozapine in adulthood

Jing Qiao, Qinglin Zhang, Ming Li

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

This preclinical study investigated how a short-term risperidone treatment in adolescence impacts antipsychotic response to olanzapine and clozapine in adulthood. Antipsychotic effect was indexed by a drug's suppressive effect on avoidance responding in a rat conditioned avoidance response (CAR) model. Male adolescent Sprague-Dawley rats were first treated with risperidone (1.0. mg/kg, sc) or sterile water and tested in the CAR model for 5 consecutive days from postnatal days P 40 to 44. After they became adults (~. P 80-84), they were switched to olanzapine (0.5. mg/kg, sc), clozapine (5.0. mg/kg, sc) or vehicle treatment and tested for avoidance for 5. days. During the adolescent period, repeated risperidone treatment produced a persistent inhibition of avoidance response. Throughout the 5. days of adulthood drug testing, rats previously treated with risperidone in adolescence made significantly fewer avoidance responses than the vehicle ones when they all were switched to olanzapine, indicating a risperidone-induced enhancement of behavioral sensitivity to olanzapine. In contrast, when switched to clozapine, rats previously treated with risperidone made significantly more avoidance responses than the vehicle rats, indicating a risperidone-induced decrease of behavioral sensitivity to clozapine. Performance in the prepulse inhibition of acoustic startle response in adulthood was not altered by adolescent risperidone treatment. Collectively, adolescent risperidone exposure induced a long-term change in behavioral sensitivity to other atypical antipsychotic drugs, with the specific direction of change (i.e., increase or decrease) dependent on the drug to be switched to. These long-lasting changes are likely mediated by drug-induced neuroplastic changes and may also have significant clinical implications for antipsychotic treatment of chronic patients with an early onset of psychotic symptoms.

Original languageEnglish (US)
Pages (from-to)177-185
Number of pages9
JournalProgress in Neuro-Psychopharmacology and Biological Psychiatry
Volume48
DOIs
StatePublished - Jan 3 2014

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olanzapine
Risperidone
Clozapine
Antipsychotic Agents
Therapeutics
Pharmaceutical Preparations
Startle Reflex
Acoustics

Keywords

  • Adolescence
  • Clozapine
  • Conditioned avoidance response
  • Olanzapine
  • Risperidone
  • Sensitization

ASJC Scopus subject areas

  • Pharmacology
  • Biological Psychiatry

Cite this

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title = "Long-term impacts of adolescent risperidone treatment on behavioral responsiveness to olanzapine and clozapine in adulthood",
abstract = "This preclinical study investigated how a short-term risperidone treatment in adolescence impacts antipsychotic response to olanzapine and clozapine in adulthood. Antipsychotic effect was indexed by a drug's suppressive effect on avoidance responding in a rat conditioned avoidance response (CAR) model. Male adolescent Sprague-Dawley rats were first treated with risperidone (1.0. mg/kg, sc) or sterile water and tested in the CAR model for 5 consecutive days from postnatal days P 40 to 44. After they became adults (~. P 80-84), they were switched to olanzapine (0.5. mg/kg, sc), clozapine (5.0. mg/kg, sc) or vehicle treatment and tested for avoidance for 5. days. During the adolescent period, repeated risperidone treatment produced a persistent inhibition of avoidance response. Throughout the 5. days of adulthood drug testing, rats previously treated with risperidone in adolescence made significantly fewer avoidance responses than the vehicle ones when they all were switched to olanzapine, indicating a risperidone-induced enhancement of behavioral sensitivity to olanzapine. In contrast, when switched to clozapine, rats previously treated with risperidone made significantly more avoidance responses than the vehicle rats, indicating a risperidone-induced decrease of behavioral sensitivity to clozapine. Performance in the prepulse inhibition of acoustic startle response in adulthood was not altered by adolescent risperidone treatment. Collectively, adolescent risperidone exposure induced a long-term change in behavioral sensitivity to other atypical antipsychotic drugs, with the specific direction of change (i.e., increase or decrease) dependent on the drug to be switched to. These long-lasting changes are likely mediated by drug-induced neuroplastic changes and may also have significant clinical implications for antipsychotic treatment of chronic patients with an early onset of psychotic symptoms.",
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