Risperidone induces long-lasting changes in the conditioned avoidance response and accumbal gene expression selectively in animals treated as adolescents

Moe, Aung Aung Kywe, Kurniawan, Nyoman D., Alexander, Suzanne, Cui, Xiaoying, Burne, Thomas H. J. and Eyles, Darryl W. (2016) Risperidone induces long-lasting changes in the conditioned avoidance response and accumbal gene expression selectively in animals treated as adolescents. Neuropharmacology, 108 264-274. doi:10.1016/j.neuropharm.2016.04.035

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Author Moe, Aung Aung Kywe
Kurniawan, Nyoman D.
Alexander, Suzanne
Cui, Xiaoying
Burne, Thomas H. J.
Eyles, Darryl W.
Title Risperidone induces long-lasting changes in the conditioned avoidance response and accumbal gene expression selectively in animals treated as adolescents
Journal name Neuropharmacology   Check publisher's open access policy
ISSN 1873-7064
0028-3908
Publication date 2016-09-01
Year available 2016
Sub-type Article (original research)
DOI 10.1016/j.neuropharm.2016.04.035
Open Access Status Not yet assessed
Volume 108
Start page 264
End page 274
Total pages 11
Place of publication Kidlington, Oxford, United Kingdom
Publisher Pergamon Press
Collection year 2017
Language eng
Formatted abstract
Adolescence is a period of dynamic remodeling and maturation in the brain. Exposure to psychotropic drugs during adolescence can potentially alter neural maturation in the adolescent brain subsequently altering neural function at maturity. In this regard, antipsychotic drugs (APDs) are important given a notable global increase in prescription of these APDs to adolescents for a variety of behavioural symptoms and conditions over the past twenty years. However, there is a paucity of data on the long-term consequences of APDs on the adolescent brain. In this preclinical study, we have examined whether the adolescent brain is more susceptible than the adult brain to long-term neural changes induced by risperidone, which is the APD most frequently prescribed to adolescents. Rats were chronically treated (21 days) with 1.3 mg/kg/day risperidone or vehicle either as adolescents (postnatal day (PND) 36-56)) or adults (PND80-100). Behaviour was assessed using the well-described suppression of the conditioned avoidance response (CAR) by APDs. We examined CAR after all animals had reached maturity (PND127). We show that mature rats treated with risperidone as adolescents had increased CAR suppression compared to adults when rechallenged with this same drug. In the nucleus accumbens, significant downregulation of serotonergic 5HT2A receptors and catechol-o-methyl transferase mRNA levels was observed only in the adolescent treated animals. Impaired 5HT2A receptor signaling may explain the increased CAR suppression observed in rats treated with risperidone as adolescents. Magnetic resonance imaging (MRI), however, did not detect any risperidone-induced long-term brain structural change at maturity. These findings confirm that APD administration during adolescence may produce long-term behavioural and neurochemical alterations.
Keyword 5HT2A receptor
Adolescent
Animal model
Antipsychotic drugs
Conditioned avoidance response
Long-term effects
MRI
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
Queensland Brain Institute Publications
Centre for Advanced Imaging Publications
 
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