Level Of Individual Differences In A Population Of Sprague Dawely Rats In A Behavioral Test Battery And Effect Of Dopaminergic Signaling Modulation On Spatial Reference Memory As Well As Prefrontal Cortex Protein Expression

Level of Individual Differences in a Population of Sprague Dawely Rats in arnBehavioral Test Battery and Effect of Dopaminergic Signaling Modulation onrnSpatial Reference Memory as well as Prefrontal Cortex Protein ExpressionrnrnDaniel Daba Feyissa, rnAddis Ababa University, 2019 rnrnSpatial reference memory is known to be modulated by the dopaminergic system involvingrndifferent brain regions with projections to the hippocampus. The roles of dopamine type 1 and 2rnreceptors are reported to be different upon learning or memory in an activation and taskrndependent manner. While the hippocampus is traditionally considered a key structure in thernformation of spatial memories, recent data has converged on the importance of its connections tornthe prefrontal cortex supporting memory consolidation, as well as controlling memory retrieval.rnHowever, the role of dopamine signaling on prefrontal cortex-mediated spatial reference memoryrnconsolidation, and especially on proteomic changes after learning tasks, remains poorlyrninvestigated. On the other hand, different early pre-and postnatal experiences and environmentalrncomplexity support individual behavior, physiology, and molecular processes during adulthood.rnFor these reasons, it is difficult to generalize between different laboratories but individualityrnshould be estimated for each local population of animals and may then provide more reliablernresults in animal models of mental and cognitive diseases and individual vulnerability.rn rnThe current research is focused on investigation of the role of dopamine type 1 and 2 likernreceptor signaling on spatial reference memory in “simple” and “difficult” hole-board paradigmrnas well as the change in proteomic landscape in prefrontal cortex. Furthermore, the currentrnresearch helps to investigate the level of individual differences in a given population of SpragueDawleyrnrnrats which may indirectly provide some evidences about whether dopaminergicrnsignaling improves spatial reference learning and memory through direct effect or throughrnincreasing motivation of animals for search of the reward. rnBriefly for the investigation of the level of individual differences in a population of SpragueDawleyrnrnrats, 162 naïve rats were underwent a behavioral test battery including commonly usedrntest paradigm for spatial learning and memory (hole-board) and different behavioral patterns testrnparadigms such as open field, elevated plus maze, forced swim test as well as rota rod for motorrnabilities. And to assess the contribution of Drn1rn and Drn -like dopamine receptor signaling on spatialrnlearning and memory in a food rewarded hole-board task, a canula was implanted surgically intornright side lateral ventricle of 60 rats’ age 12-13 weeks. The rats were grouped into 6 groups withrn10 rats each. The first four groups were treated with SKF-81297 (1μg and 5μg) and Sumanirole rn2rn(1μg and 5μg) through intracerebroventricular infusion once 30 min prior to daily trainingrnsessions. The other two groups were treated with 1μg of SCH 23390 and Remoxipride followingrnsimilar procedure. D1 agonist at one dosage (5µg) was used in a more demanding hole-board rntask. In addition, proteomics studies were carried out to identify proteins that could be influencedrnby the dopaminergic signaling during the spatial reference memory acquisition and consolidationrnin a more demanding hole-board task.rnrnThe high dimensional behavioral results from behavioral test batteries mentioned above werernreduced to fewer components associated with spatial cognition, motivation, anxiety andrndepression-like behaviors. The behavioural battery test indicated that, 24 % showed a high, 19 %rna low and 57 % an intermediate intrinsic state of motivation. The largest 'low' portion (41%) wasrngiven for the factor cognition and the largest 'high' portion (29%) for the intrinsic anxiety. Thus,rnalmost every third rat was intrinsically at a high level in the population. Because the animalsrnwere intact, untreated and experimentally naïve the results reflect trait patterns of behavior andrnthus individuality. On the other hand, the hole-board spatial reference memory assessmentrnrevealed that D1R agonism induced persistent enhancement of performance, whereas D1R rnantagonism had no significant effect on spatial reference memory formation. D2R agonist andrnantagonist exerted no effects. Phase specific comparisons revealed an enhancement of spatialrnacquisition in the presence of the D1R but not D2R agonism on acquisition, but not duringrnretention. The D1R agonist tested in the hole-board task with increased “difficulty” revealed thatrnD1R agonist treated animals performed significantly better during all training phases, withrnresults better resolved than in the “easy” task. Additionally, proteomic analysis of the prefrontalrncortex revealed ninety six proteins to be regulated by D1R agonism, from which 35 were rncorrelated with behavioral performance. Obtained targets were grouped by function, showingrnsynaptic transmission, synaptic remodeling, and dendritic spine morphology as the majorrnfunctional classes affected.rnrn The behavioral test batteries pointed out that an experimenter recruiting experimental samplesrncan expect about ≥24 % probability to have intrinsically high animals in terms of anxiety,rncognitive, motivation and depressive like behaviours in the sample. Furthermore, activation ofrnD1R signaling during spatial acquisition and consolidation improved reference memory indexrndepending on the task difficulty, with greater effect in a “difficult” task and altered the proteomernlandscape of the prefrontal cortex indicative of massive organizational synaptic restructuring.

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