Risperidone induces long-lasting changes in the conditioned avoidance response and accumbal gene expression selectively in animals treated as adolescents. (September 2016)

• Record Type: Journal Article
• Authors: Moe, Aung Aung Kywe; Kurniawan, Nyoman D.; Alexander, Suzanne; Cui, Xiaoying; Burne, Thomas H.J.; Eyles, Darryl W.
• Is Part Of: Neuropharmacology. Volume 108(2016)
• Page Start: 264
• Page End: 274
• Publication Date: 2016-09
• Subjects: Antipsychotic drugs -- Animal model -- Adolescent -- Conditioned avoidance response -- Long-term effects -- 5HT2A receptor -- MRI; Neuropsychopharmacology -- Periodicals; Autonomic Agents -- Periodicals; Neuropsychopharmacologie -- Périodiques; Neuropsychopharmacology; Periodicals; Electronic journals; 615.78
• DOI: 10.1016/j.neuropharm.2016.04.035
• Languages: English
• ISSNs: 0028-3908

Abstract

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. Highlights: Adolescent and adult rats were subjected to the same regimen of chronic 21-day risperidone treatment. After a lengthy drug-free interval, behavioural and neurochemical changes selective to adolescent treatment were observed. Downregulated accumbal 5HT2 A receptors may underlie the increased response in CAR in adolescent risperidone-treated rats. Rats treated in adolescence showed increased drug response in conditioned avoidance response (CAR) in adulthood.