ABSTRACT
Objectives@#ZZKetamine has been reported to have antidepressant effects or psychotomimetic effects. The aim of this study was to investigatethe behavioral effects of ketamine treatment at various sub-anesthetic doses in adolescent and adult naïve mice. @*Methods@#ZZIn each experiment for adolescent and adult mice, a total of 60 male Institute of Cancer Research mice were randomly dividedinto 6 groups, which were intraperitoneally treated with physiological saline, 10, 20, 30, 40, and 50 mg/kg ketamine for consecutive3 days. At 1 day after last injection, the locomotor and depressive-like behaviors were evaluated in mice, using open field test (OFT)and forced swim test (FST), respectively. @*Results@#ZZIn case of adolescent mice, ketamine dose was negatively correlated with total distance traveled in the OFT (Spearman’srho = -0.27, p = 0.039). In case of adult mice, we found significant positive correlation between ketamine dose and duration of immobilityin the FST (Spearman’s rho = 0.45, p < 0.001). Immobility time in the 50 mg/kg ketamine-treated mice was significantly higher comparedto the saline-treated mice (Dunnett’s post-hoc test, p = 0.012). @*Conclusions@#ZZWe found that the repeated treatment with ketamine could decrease the locomotor or prolong the duration of immobilityin mice as the dose of ketamine increased. Our findings suggest that sub-anesthetic doses of ketamine might induce schizophrenia-like negative symptoms but not antidepressant effects in naïve laboratory animals.
ABSTRACT
Objectives@#ZZKetamine has been reported to have antidepressant effects or psychotomimetic effects. The aim of this study was to investigatethe behavioral effects of ketamine treatment at various sub-anesthetic doses in adolescent and adult naïve mice. @*Methods@#ZZIn each experiment for adolescent and adult mice, a total of 60 male Institute of Cancer Research mice were randomly dividedinto 6 groups, which were intraperitoneally treated with physiological saline, 10, 20, 30, 40, and 50 mg/kg ketamine for consecutive3 days. At 1 day after last injection, the locomotor and depressive-like behaviors were evaluated in mice, using open field test (OFT)and forced swim test (FST), respectively. @*Results@#ZZIn case of adolescent mice, ketamine dose was negatively correlated with total distance traveled in the OFT (Spearman’srho = -0.27, p = 0.039). In case of adult mice, we found significant positive correlation between ketamine dose and duration of immobilityin the FST (Spearman’s rho = 0.45, p < 0.001). Immobility time in the 50 mg/kg ketamine-treated mice was significantly higher comparedto the saline-treated mice (Dunnett’s post-hoc test, p = 0.012). @*Conclusions@#ZZWe found that the repeated treatment with ketamine could decrease the locomotor or prolong the duration of immobilityin mice as the dose of ketamine increased. Our findings suggest that sub-anesthetic doses of ketamine might induce schizophrenia-like negative symptoms but not antidepressant effects in naïve laboratory animals.
ABSTRACT
OBJECTIVE: This study aimed to investigate the long-term effects of aripiprazole treatment during adolescence on behavior, cognitive function, and dopamine D2 receptor (D2R) expression in adult rats. METHODS: Adolescent male Sprague-Dawley rats were injected intraperitoneally with aripiprazole, risperidone, or vehicle control for 3 weeks (postnatal day 36–56). After a 2-week washout period, locomotion, anxiety, and spatial working memory were evaluated in adulthood (postnatal day 71–84), using an open field test, elevated plus maze, and Y-maze, respectively. In addition, we assessed D2R levels in the dorsolateral and medial prefrontal cortex (PFC), dorsal and ventral striatum, and hippocampus using western blot analysis. RESULTS: Spontaneous alternation performance (SAP) in the Y-maze, a measure of spatial working memory, differed significantly among the 3 groups (F = 3.89, p = 0.033). A post-hoc test confirmed that SAP in the aripiprazole group was significantly higher than that in the risperidone group (post-hoc test p = 0.013). D2R levels in the medial PFC (F = 8.72, p = 0.001) and hippocampus (F = 13.54, p < 0.001) were different among the 3 groups. D2R levels in the medial PFC and hippocampus were significantly lower in the aripiprazole-treated rats than that in the risperidone-treated rats (post-hoc test p = 0.025 and p < 0.001, respectively) and controls (post-hoc test p < 0.001, all). CONCLUSION: This study showed that aripiprazole treatment in adolescence could influence cognitive function and dopaminergic neurotransmission into early adulthood.