Increased Aggression, Improved Spatial Memory, and Reduced Anxiety-Like Behaviour in Adult Male Mice Exposed to Fluoxetine Early in Life

Veronika Kiryanova, Richard H. Dyck
2014 Developmental Neuroscience  
Rationale: Fluoxetine (Flx; brand names Prozac, Sarafem, Rapiflux), a selective serotonin reuptake inhibitor, is prescribed for the treatment of depression in pregnant women; however, this commonly prescribed medication could affect fetal brain development as Flx crosses the placenta. The available data concerning the anatomical and behavioural consequences of perinatal exposure to Flx during early development on adult behaviour are limited and often contradictory. Objectives: To further
more » ... te the long-term behavioural effects of altering 5-HT during development, we examined the effects of perinatal Flx exposure on the behaviour of male mice as adults. Methods: Dams were treated with approximately 25 mg/kg/day of Flx from embryonic day 15 to postnatal day 12, and the behaviour of the adult offspring was assessed. Results: We found that perinatal Flx exposure leads to increased aggression, improved spatial memory, and reduced anxiety-like behaviour. This exposure did not cause memory deficits, changes in sensory processing, or changes in gross motor function. Conclusions: Our results suggest that while perinatal exposure to Flx may have long-term effects on adult behaviour, these effects appear limited and not necessarily detrimental. 398 Measurement of Flx, NorFlx, and Serotonin in Pup Brains Sample Collection Pup brains were collected from male and female pups at P0 (control: n = 6, from 3 litters; Flx: n = 9, from 4 litters) and P12 (control: n = 6, from 3 litters; Flx: n = 6, from 3 litters). After decapitation, the brain was removed, the spinal cord was severed posterior to the cerebellum, and the olfactory bulbs were removed. Cortical structures were peeled away from the thalamus. For the brains dissected at P0, cortical (cortex and hippocampus) and subcortical structures (thalamus, midbrain, hindbrain, and cerebellum) were individually flash-frozen in 1.5-ml microcentrifuge tubes. For the P12 brains, after the cortical structures were peeled away from the underlying thalamus, the subcortical pieces were bisected between the cerebellum and inferior colliculus, and the three resulting brain areas were separately frozen and analysed separately as (1) cortex and hippocampus, (2) thalamus/midbrain, and (3) hindbrain/cerebellum. Sample Preparation The sample preparation method was based on Raap et al. [47] . The samples were homogenized using an ultrasonic probe tissue disruptor (Virtis VirSonic 50) in 10 volumes (1 ml/100 mg tissue) of ice-cold acetone (1 M formic acid, 85: 15) containing 100 ng/ml norfluvoxamine as an internal standard. They were then centrifuged at high speed (15,000 rpm, 5 min), and 200 μl of supernatant was transferred to a clean centrifuge tube and dried down at room temperature in a vacuum centrifuge (about 20 min). Then, they were reconstituted in 100 μl of 50% methanol. Effects of Exposure to Flx Early in Life on Adult Male Mice Dev Neurosci 2014;36:396-408
doi:10.1159/000363102 pmid:25115143 fatcat:v7woajqskrhe5e3qwbrtd44w5q