作者: Robert K. McNamara , Jessica A. Able , Yanhong Liu , Ronald Jandacek , Therese Rider
DOI: 10.1016/J.PBB.2013.09.010
关键词: Fluoxetine 、 Fatty acid 、 Serotonin reuptake inhibitor 、 Internal medicine 、 Behavioural despair test 、 Docosahexaenoic acid 、 Neurochemical 、 Serotonin 、 Biology 、 Endocrinology 、 Omega 3 fatty acid
摘要: Abstract While translational evidence suggests that long-chain omega-3 fatty acid status is positively associated with the efficacy of selective serotonin reuptake inhibitor drugs, neurochemical mechanisms mediating this interaction are not known. Here, we investigated effects dietary ( n -3) insufficiency on and behavioral chronic fluoxetine (FLX) treatment. Female rats were fed diets (CON, n = 56) or without (DEF, n = 40) -3 acids during peri-adolescent development (P21–P90), one half each group was administered FLX (10 mg/kg/day) for 30 days (P60–P90) prior to testing. In adulthood (P90), regional brain (5-HT) 5-hydroxyindoleacetic (5-HIAA) concentrations, presynaptic markers 5-HT neurotransmission, responses in forced swim test (FST), plasma norfluoxetine (NFLX) concentrations investigated. Peri-adolescent led significant reductions cortical docosahexaenoic (DHA, 22:6 composition DEF (− 25%, p ≤ 0.0001) DEF + FLX (− 28%, rats. Untreated exhibited significantly lower 5-HIAA/5-HT ratios compared untreated CON rats, but similar FST. both treatment similarly decreased 5-HIAA ratio hypothalamus, hippocampus, nucleus accumbens, brainstem tryptophan hydroxylase-2 mRNA expression, immobility FLX-induced reduction prefrontal cortex blunted Although NFLX levels different NFLX/FLX These preclinical data demonstrate deficiency does reduce central turnover behavior FST female