Differential behavioural and neurochemical outcomes from chronic paroxetine treatment in adolescent and adult rats: a model of adverse antidepressant effects in human adolescents?

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dc.contributor.authorKaranges, Een_AU
dc.contributor.authorLi, KMen_AU
dc.contributor.authorMotbey, CPen_AU
dc.contributor.authorCallaghan, PDen_AU
dc.contributor.authorKatsifis, Aen_AU
dc.contributor.authorMcGregor, ISen_AU
dc.date.accessioned2013-12-02T21:37:25Zen_AU
dc.date.available2013-12-02T21:37:25Zen_AU
dc.date.issued2011-05-01en_AU
dc.date.statistics2013-12-03en_AU
dc.description.abstractSelective serotonin reuptake inhibitor use is associated with increased risk of suicidal ideation in adolescent humans, yet the neuropharmacological basis of this phenomenon is unknown. Consequently, we examined the behavioural and neurochemical effects of chronic paroxetine (PRX) treatment in adult and adolescent rats. Rats received PRX in their drinking water (target dose 10 mg/kg) for 22 d, during which time they were assessed for depression- and anxiety-like behaviours. Subsequent ex-vivo analyses examined serum PRX concentrations, striatal neurotransmitter content, and regional serotonin and dopamine transporter (SERT, DAT) binding density. After 11–12 d treatment, PRX-treated adolescent rats showed a significant inhibition of social interaction while adults were unaffected. After 19–20 d treatment, adolescents failed to show an antidepressant-like effect of PRX treatment on the forced swim test (FST), while PRX-treated adults showed a typical decrease in immobility and increase in swimming. Two PRX-treated adolescents died unexpectedly after the FST suggesting a compromised response to physical stress. Despite their greater apparent adverse reaction to the drug, adolescents had significantly lower plasma PRX than adults at day 22 of treatment. Chronic PRX treatment had similar effects in adults and adolescents on striatal 5-HT (unchanged relative to controls) and 5-HIAA levels (decreased), while markers of dopaminergic function (DOPAC, HVA, DA turnover) were increased in adults only. SERT density was up-regulated in the amygdala in PRX-treated adolescents only while DAT density in the nucleus accumbens was down-regulated only in PRX-treated adults. These data suggest that the immature rat brain responds differently to PRX and that this might be of use in modelling the atypical response of human adolescents to antidepressants. The age-specific PRX-induced changes in dopaminergic markers and SERT and DAT binding provide clues as to the neural mechanisms underlying adverse PRX effects in adolescent humans. © 2011, Cambridge University Pressen_AU
dc.identifier.citationKaranges, E., Li, K., Motbey, C., Callaghan, P., Katsifis, A., & McGregor, I. (2011). Differential behavioural and neurochemical outcomes from chronic paroxetine treatment in adolescent and adult rats: a model of adverse antidepressant effects in human adolescents?. International Journal of Neuropsychopharmacology, 14 (4), 491-504. doi:10.1017/S146114571100006Xen_AU
dc.identifier.govdoc5288en_AU
dc.identifier.issn1461-1457en_AU
dc.identifier.issue4en_AU
dc.identifier.journaltitleInternational Journal of Neuropsychopharmacologyen_AU
dc.identifier.pagination491-504en_AU
dc.identifier.urihttp://dx.doi.org/10.1017/S146114571100006Xen_AU
dc.identifier.urihttp://apo.ansto.gov.au/dspace/handle/10238/5056en_AU
dc.identifier.volume14en_AU
dc.language.isoenen_AU
dc.publisherInternational Journal of Neuropsychopharmacology.en_AU
dc.subjectAdolescentsen_AU
dc.subjectAntidepressantsen_AU
dc.subjectRatsen_AU
dc.subjectCerebral cortexen_AU
dc.subjectReceptorsen_AU
dc.subjectSerotoninen_AU
dc.titleDifferential behavioural and neurochemical outcomes from chronic paroxetine treatment in adolescent and adult rats: a model of adverse antidepressant effects in human adolescents?en_AU
dc.typeJournal Articleen_AU
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