BackgroundChanges in synaptic structure and efficacy including dendritic spine number and morphology have been shown to underlie neuronal activity and size. Moreover, the shapes of individual dendritic spines were proposed to correlate with their capacity for structural change. Spine numbers and morphology were reported to parallel memory formation in the rat using a water maze but, so far, there is no information on spine counts or shape in the radial arm maze (RAM), a frequently used paradigm for the evaluation of complex memory formation in the rodent.Methods24 male Sprague-Dawley rats were divided into three groups, 8 were trained, 8 remained untrained in the RAM and 8 rats served as cage controls. Dendritic spine numbers and individual spine forms were counted in CA1, CA3 areas and dentate gyrus of hippocampus using a DIL dye method with subsequent quantification by the Neuronstudio software and the image J program.ResultsWorking memory errors (WME) and latency in the RAM were decreased along the training period indicating that animals performed the task. Total spine density was significantly increased following training in the RAM as compared to untrained rats and cage controls. The number of mushroom spines was significantly increased in the trained as compared to untrained and cage controls. Negative significant correlations between spine density and WME were observed in CA1 basal dendrites and in CA3 apical and basal dendrites. In addition, there was a significant negative correlation between spine density and latency in CA3 basal dendrites.ConclusionThe study shows that spine numbers are significantly increased in the trained group, an observation that may suggest the use of this method representing a morphological parameter for memory formation studies in the RAM. Herein, correlations between WME and latency in the RAM and spine density revealed a link between spine numbers and performance in the RAM.

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Animal models for anxiety, depressive-like and cognitive diseases or aging often involve testing of subjects in behavioral test batteries. The large number of test variables with different mean variations and within and between test correlations often constitute a significant problem in determining essential variables to assess behavioral patterns and their variation in individual animals as well as appropriate statistical treatment. Therefore, we applied a multivariate approach (principal component analysis) to analyse the behavioral data of 162 male adult Sprague-Dawley rats that underwent a behavioral test battery including commonly used tests for spatial learning and memory (holeboard) and different behavioral patterns (open field, elevated plus maze, forced swim test) as well as for motor abilities (Rota rod). The high dimensional behavioral results were reduced to fewer components associated with spatial cognition, general activity, anxiety-, and depression-like behavior and motor ability. The loading scores of individual rats on these different components allow an assessment and the distribution of individual features in a population of animals. The reduced number of components can be used also for statistical calculations like appropriate sample sizes for valid discriminations between experimental groups, which otherwise have to be done on each variable. Because the animals were intact, untreated and experimentally naïve the results reflect trait patterns of behavior and thus individuality. The distribution of animals with high or low levels of anxiety, depressive-like behavior, general activity and cognitive features in a local population provides information of the probability of their appeareance in experimental samples and thus may help to avoid biases. However, such an analysis initially requires a large cohort of animals in order to gain a valid assessment.

A series of drugs have been reported to increase memory performance modulating the dopaminergic system and herein modafinil was tested for its working memory (WM) enhancing properties. Reuptake inhibition of dopamine, serotonin (SERT) and norepinephrine (NET) by modafinil was tested. Sixty male Sprague–Dawley rats were divided into six groups (modafinil-treated 1–5–10 mg/kg body weight, trained and untrained and vehicle treated trained and untrained rats; daily injected intraperitoneally for a period of 10 days) and tested in a radial arm maze (RAM), a paradigm for testing spatial WM. Hippocampi were taken 6 h following the last day of training and complexes containing the unphosphorylated or phosphorylated dopamine transporter (DAT-CC and pDAT-CC) and complexes containing the D1–3 dopamine receptor subunits (D1–D3-CC) were determined. Modafinil was binding to the DAT but insignificantly to SERT or NET and dopamine reuptake was blocked specifically (IC50 = 11.11 μM; SERT 1547 μM; NET 182 μM). From day 8 (day 9 for 1 mg/kg body weight) modafinil was decreasing WM errors (WMEs) in the RAM significantly and remarkably at all doses tested as compared to the vehicle controls. WMEs were linked to the D2R-CC and the pDAT-CC. pDAT and D1–D3-CC levels were modulated significantly and modafinil was shown to enhance spatial WM in the rat in a well-documented paradigm at all the three doses and dopamine reuptake inhibition with subsequent modulation of D1–3-CC is proposed as a possible mechanism of action.

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