Enrichment Discrimination Behavior in Spontaneously Hypertensive Rats

Abstract

Objectives: 1) To reveal, among spontaneously hypertensive rats, subpopulations that diverge in attention to objects enriching an empty cross-maze; 2) To evaluate effect of clinically efficient drug for treatment of attention deficiency atomoxetine on the attention to environmental cues in attentionally-low rats. Method: A novel paradigm that provides measure of attention towards enriching objects independent of general locomotor activity and spatial orientation is employed. The apparatus consists of 4-arm radial maze, two arms of which contain objects (enriched compartments). Animals exploring the objects typically stay longer in enriched parts of maze than in empty arms and have a higher score of enrichment discrimination ratio. Results: Frequency distribution of the enrichment discrimination ratio had clear bimodal shape that differed significantly from normal distribution suggesting the existence of subpopulations of attentionally-low and -high individuals. The attentionally-low phenotype did not show inferiority in spatial orientation as compared with attentionally-high phenotype. The phenotypes did not differ from each other in measures of locomotor activity and blood pressure. Atomoxetine (3 mg/kg, orally, once daily for 4 days) enhanced enrichment discrimination in animals of attentionally-low phenotype. Single administration of the drug was ineffective. Conclusion: Population of spontaneously hypertensive rat includes two phenotypes of attentionally-low and -high individuals. Subchronic atomoxetine ameliorates attention to environmental cues in attentionally-low rats. The enrichment discrimination test could be useful in studies of neurobiology of attention deficit condition and for screening of novel drug candidates.

Effect of Atomoxetine on Behavior of Outbred Mice in the Enrichment Discrimination Test

“…The findings of the present study in mice generalize and extend results previously reported in spontaneously hypertensive rats [18]. Both the species include individuals of attentionally-low and -high phenotypes.…”

“…The sequence and timing of arms visited were recorded directly into a personal computer by the use of Behavset 3.0 software. The floor and the objects in arms were cleaned thoroughly with paper towel damped in 70% ethanol and were air-dried after each trial [18]. The position of the objects in a pair of opposite arm (#1 and #3, or #2 and #4) was alternated in a quasi-random order.…”

“…It has been reported that the spontaneously hypertensive rat strain include subpopulations of, so-called, impulsive and non-impulsive individuals [16,17]. Recently, the rat strain was also found to be nonhomogeneous with regard to attention in paradigm of enrichment discrimination that does not involve rule learning and provides separate measures of attention towards enriching objects (ED-ratio), general locomotor activity and spatial orientation [18]. The latter is considered as belonging to cognitive domain that parallel Cattell's general fluid intelligence [19,20] and has been used for assessment of cognition enhancing drugs [21][22][23].…”

“…The latter is considered as belonging to cognitive domain that parallel Cattell's general fluid intelligence [19,20] and has been used for assessment of cognition enhancing drugs [21][22][23]. The at-tentionally-low and -high subpopulations did not differ from each other in measures of locomotor activity and blood pressure [18]. Also, the attentionally-high phenotype, as compared with the attentionally-low one, did not show superiority in ability for spatial orientation.…”