Decreased anxiety in mice lacking the organic cation transporter 3.

The organic cation transporter 3 (OCT3; synonymous: extraneuronal monoamine transporter, EMT, Slc22a3) encodes an isoform of the organic cation transporters and is expressed widely across the whole brain. OCTs are a family of high-capacity, bidirectional, multispecific transporters of organic cations. These also include serotonin, dopamine and norepinephrine making OCTs attractive candidates for a variety of neuropsychiatric disorders including anxiety disorders. OCT3 has been implicated in termination of monoaminergic signalling in the central nervous system. Interestingly, OCT3 mRNA is however also significantly up-regulated in the hippocampus of serotonin transporter knockout mice where it might serve as an alternative reuptake mechanism for serotonin. The examination of the behavioural phenotype of OCT3 knockout mice thus is paramount to assess the role of OCT3. We have therefore subjected mice lacking the OCT3 gene to a comprehensive behavioural test battery. While cognitive functioning in the Morris water maze test and aggression levels measured with the resident-intruder paradigm were in the same range as the respective control animals, OCT3 knockout animals showed a tendency of increased activity and were significantly less anxious in the elevated plus-maze test and the open field test as compared to their respective wild-type controls arguing for a role of OCT3 in the regulation of fear and anxiety, probably by modulating the serotonergic tone in limbic circuitries.

The COGITAT holeboard system as a valuable tool to assess learning, memory and activity in mice.

The comprehensive and stress-free assessment of various aspects of learning and memory is a prerequisite to evaluate mouse models for neuropsychiatric disorders such as Alzheimer's disease or attention deficit/hyperactivity disorder (ADHD). COGITAT is an automated holeboard system allowing simultaneous assessment of spatial working and reference-memory performance which we have adapted in this study to enable its usage with mice. The holeboard apparatus consists of an open-field chamber with a 25-hole floor insert, each hole being monitored by infrared light beams, located on three different levels, allowing the distinction between visits of holes, i.e. the animal reaches the bottom of the hole, or inspections, which means only superficial exploration of the hole. Across trials, animals learn a pattern of five baited holes. Here, we show that C57BL/6 mice readily acquire this task within 5 days when submitted to six trials per day. A number of individual parameters - overall exploratory activity, number of visits into or inspections of holes, number of baited, unbaited, or previously baited holes visited or inspected, reinspections of or revisits into any holes, number of pellets eaten, time to find pellets, and reference and working memory errors-are obtained simultaneously and results are immediately available after the end of each experiment. The muscarinic antagonist scopolamine impaired task performance, while the cognitive enhancer metrifonate (an acetylcholinesterase inhibitor) reduced error rates. Overall, our data indicate that this spatial learning task will be useful to characterize spatial memory in various genetic or pharmacological mouse models.