title: Risperidone in ultra low dose protects against stress in the rodent cold restraint model by modulating stress pathways.
abstract: The present investigation evaluates the anti-stress activity of risperidone (RIS) in the cold restraint stress (CRS) model and related stress pathways. Rats were pretreated with RIS (0.1 and 1.0 mg/kg) for 21 days before subjecting to CRS. Ultra low dose of RIS (ULD; 0.1 mg/kg) in contrast to higher dose (1.0 mg/kg) significantly reduced stress in terms of ulcer index. ULD also reversed stress-induced increase in plasma corticosterone and norepinephrine levels used as markers for the function of hypothalamo-pituitary-adrenal (HPA) axis and sympathetic nervous system (SNS) respectively. ULD caused dose and brain region (hippocampus, prefrontal cortex and striatum) specific changes to stress-induced perturbations of serotonin, dopamine and its metabolites indicating modulation of brain monoaminergic system (BMS). ULD did not show any extrapyramidal side effects. Thus, the anti-stress effect ULD is probably mediated through the HPA axis, SNS and BMS. The study indicates a potential use of ULD in stress disorders.
authors.affiliation: Neurotherapeutics Lab, Department of Pharmaceutics, Institute of Technology, Banaras Hindu University, Varanasi 221005, India. saibliss@hotmail.com
authors.forename: Sairam
authors.initials: S
authors.lastname: Krishnamurthy
authors.forename: Debapriya
authors.initials: D
authors.lastname: Garabadu
authors.forename: Nagannathahalli Ranga
authors.initials: NR
authors.lastname: Reddy
authors.forename: Keerikkattil P
authors.initials: KP
authors.lastname: Joy
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism; D002375:Catalepsy / Q000188:drug therapy; D003080:Cold Temperature; D003345:Corticosterone / Q000097:blood; D004298:Dopamine / Q000378:metabolism; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000502:physiology; D008297:Male; D009483:Neuropsychological Tests; D009638:Norepinephrine / Q000097:blood; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000502:physiology; D011897:Random Allocation; D051381:Rats; D012149:Restraint, Physical / Q000523:psychology*; D018967:Risperidone / Q000494:pharmacology / Q000627:therapeutic use*; D012701:Serotonin / Q000378:metabolism; D013315:Stress, Psychological / Q000188:drug therapy*; D013564:Sympathetic Nervous System / Q000502:physiology
chemical_list: D014150:Antipsychotic Agents; D012701:Serotonin; D018967:Risperidone; D004298:Dopamine; D003345:Corticosterone; D009638:Norepinephrine