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 locomo- tor activity and blood pressure. Atomoxetine (3 mg/kg, orally, once daily for 4 days) enhanced enrichment discrimina- tion in animals of attentionally-low phenotype. Single administration of the drug was ineffective. Conclusion: Popula- tion 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.
Cite this paper
R. Salimov and G. Kovalev, "Enrichment Discrimination Behavior in Spontaneously Hypertensive Rats," Journal of Behavioral and Brain Science, Vol. 2 No. 4, 2012, pp. 479-484. doi: 10.4236/jbbs.2012.24056.
 American Academy of Pediatrics, “Clinical Practice Guideline: Diagnosis and Evaluation of the Child with Attention-Deficit/Hyperactivity Disorder,” Pediatrics, Vol. 105, No. 5, 2000, pp. 1158-1170.
 Y. Paloyelis, F. Rijsdijk, A. C. Wood, P. Asherson and J. Kuntsi, “The Genetic Association between ADHD Symptoms and Reading Difficulties: The Role of Inattentiveness and IQ,” Journal of Abnormal Child Psychology, Vol. 38, No. 8, 2010, pp. 1083-1095.
 K. Al-Menabbawy, A. El-Gerzawy, A. Ezzat and H. Mottawie, “Developmental, Behavioral and Genetic Factors in Correlation with Attention Deficit Hyperactivity Disorder in Egyptian Children,” Journal of Medical Sciences, Vol. 6, No. 4, 2006, pp. 569-576.
 S. Mannuzza, R.G. Klein, A. Bessler, P. Malloy and M. LaPadula, “Adult Outcome of Hyperactive Boys. Educational Achievement, Occupational Rank and Psychiatric Status,” Archives of General Psychiatry, Vol. 50, No. 7, 1993, pp. 565-576.
 P. Asherson, W. Chen, B. Craddock and E. Taylor, “Adult Attention-Deficit Hyperactivity Disorder: Recognition and treatment in General Adult Psychiatry,” The British Journal of Psychiatry, Vol. 190, No. 1, 2007, pp. 4-5.
 N. Kates, “Attention Deficit Disorder in Adults. Management in Primary Care,” Canadian Family Physician, Vol. 51, No. 1, 2005, pp. 53-59.
 F. Naderi, A. Heidarie, L. Bouron and P. Asgari, “The Efficacy of Play Therapy on ADHD, Anxiety and Social Maturity in 8 to 12 Years Aged Clientele Children of Ahwaz Metropolitan Counseling Clinics,” Journal of Applied Sciences, Vol. 10, No. 3, 2010, pp.189-195.
 J. C. Bizot, S. David and F. Trovero, “Effects of Atomoxetine, Desipramine, d-Amphetamine and Methylphenidate on Impulsivity in Juvenile Rats, Measured in a T-Maze Procedure,” Neuroscience Letters, Vol. 489, No. 1, 2011, pp. 20-24. doi:10.1016/j.neulet.2010.11.058
 E. Davids, K. Zhang, F. I. Tarazi and R. J. Baldessarini, “Animal Models of Attention-Deficit Hyperactivity Disorder,” Brain Research. Brain Research Reviews, Vol. 42, No. 1, 2003, pp. 1-21.
 T. Sagvolden, V.A. Russell, H. Aase, E.B. Johansen and M. Farshbaf, “Rodent Models of Attention-Deficit/Hyperactivity Disorder,” Biological Psychiatry, Vol. 57, No. 11, 2005, pp. 1239-1247.
 A. C. Meyer, S. Rahman, R. J. Charnigo, L. P. Dwoskin, J. C. Crabbe and M. T. Bardo, “Genetics of Novelty Seeking, Amphetamine Self-Administration and Reinstatement Using Inbred Rats,” Genes, Brain and Behavior, Vol. 9, No. 7, 2010, pp. 790-798.
 M. B. Calzavara, R. Levin, W. A. Medrano, V. Almeida and A. P. Sampaio, L. C. Barone, R. Frussa-Filho and V. C. Abílio, “Effects of Antipsychotics and Amphetamine on Social Behaviors in Spontaneously Hypertensive Rats,” Behavioural Brain Research, Vol. 225, No. 1, 2011, pp. 15-22. doi:10.1016/j.bbr.2011.06.026
 B. Langen and R. Dost, “Comparison of SHR, WKY and Wistar Rats in Different Behavioural Animal Models: Effect of Dopamine D1 and Alpha2 Agonists,” Attention Deficit and Hyperactivity Disorders, Vol. 3, No. 1, 2011, pp. 1-12. doi:10.1007/s12402-010-0034-y
 E. B. Johansen, P. R. Killeen and T. Sagvolden, “Behavioral Variability, Elimination of Responses and Delay-of-Reinforcement Gradients in SHR and WKY Rats,” Behavioral and Brain Functions, Vol. 3, 2007, pp. 60.
 J. R. Wickens, J. Macfarlane, C. Booker and N. McNaughton, “Dissociation of Hypertension and Fixed Interval Responding in Two Separate Strains of Genetically Hypertensive Rat,” Behavioural Brain Research, Vol. 152, No. 2, 2004, pp. 393-401. doi:10.1016/j.bbr.2003.10.023
 W. Danysz, A. Plaznik, O. Pucilowski, M. Plewako, M. Obersztyn and W. Kostowski, “Behavioral Studies in Spontaneously Hypertensive Rats,” Behavioral and Neural Biology, Vol. 39, No. 1, 1983, pp. 22-29.
 I. Lukaszewska and G. Niewiadomska, “The Differences in Learning Abilities between Spontaneously Hypertensive (SHR) and Wistar Normotensive Rats Are Cue Dependent,” Neurobiology of Learning and Memory, Vol. 63, No. 1, 1995, pp. 43-53. doi:10.1006/nlme.1995.1004
 A. Tamburella, V. Micale, C. Mazzola, S. Salomone and F. Drago, “The Selective Norepinephrine Reuptake Inhibitor Atomoxetine Counteracts Behavioral Impairments in Trimethyltin-Intoxicated Rats,” European Journal of Pharmacology, Vol. 683, No. 1-3, 2012, pp. 148-154.
 W. Adriani, A. Caprioli, O. Granstrem, M. Carli and G. Laviola, “The Spontaneously Hypertensive-Rat as an Animal Model of ADHD: Evidence for Impulsive and Non-Impulsive Subpopulations,” Neuroscience & Biobehavioral Reviews, Vol. 27. No. 7, 2003, pp. 639-651.
 T. E. Wooters and M. T. Bardo, “Methylphenidate and Fluphenazine, but Not Amphetamine, Differentially Affect Impulsive Choice in Spontaneously Hypertensive, Wistar-Kyoto and Sprague-Dawley Rats,” Brain Research, Vol. 1396, 2011, pp. 45-53.
 M. B. Calzavara, G. B. Lopez, V. C. Abilio, R. H. Silva and R. Frussa-Filho, “Role of Anxiety Levels in Memory Performance of Spontaneously Hypertensive Rats,” Behavioural Pharmacology, Vol. 15, No. 8, 2004, pp. 545-553. doi:10.1097/00008877-200412000-00003
 S. A. Ferguson and E. P. Gray, “Aging Effects on Elevated Plus Maze Behavior in Spontaneously Hypertensive, Wistar-Kyoto and Sprague-Dawley Male and Female Rats,” Physiology & Behavior, Vol. 85, No. 5, 2005, pp. 621-628. doi:10.1016/j.physbeh.2005.06.009
 B. Alsop, “Problems with Spontaneously Hypertensive Rats (SHR) as a Model of Attention-Deficit/Hyperactivity Disorder (AD/HD),” Journal of Neuroscience Methods, Vol. 162, No. 1-2, 2007, pp. 42-48.
 R. M. Salimov, I. I. Poletaeva, G. I. Kovalev, N. B. Salimova and R. R. Gainetdinov, “Interstrain Differences in Extrapolation Capacity and Exploration of a Cruciform Maze Correlate with Various Indices of Monoamine Metabolism in the Brain,” Zhurnal Vysshe? Nervno? Deiatenlnosti Imeni I P Pavlova, Vol. 45, No. 5, 1995, pp. 914-924.
 G. I. Kovalev, I. Firstova and R. M. Salimov, “Effects of Piracetam and Meclofenoxate on the Brain NMDA and Nicotinic Receptors in Mice with Different Exploratory Efficacy in the Cross Maze Test,” Eksperimental’naia i Klinicheskaia Farmakologiia, Vol. 71, No. 1, 2008, pp. 12-17.
 R. Salimov, N. Salimova, L. Shvets and N. Shvets, “Effect of Chronic Piracetam on Age-Related Changes of Cross-Maze Exploration in Mice,” Pharmacology Biochemistry and Behavior, Vol. 52, No. 3, 1995, pp. 637-640.
 R. M. Salimov, “Different Behavioral Patterns Related to Alcohol Use in Rodents: A Factor Analysis,” Alcohol, Vol. 17, No. 2, 1999, pp. 157-162.
 N. V. Markina, R. M. Salimov and I. I. Poletaeva, “Behavioral Screening of Two Mouse Lines Selected for Different Brain Weight,” Progress in Neuro-Psychopharmacology & Biological Psychiatry, Vol 25, No. 5, 2001, pp. 1083-1109. doi:10.1016/S0278-5846(01)00169-5
 I. I. Poletaeva, and R.M. Salimov, “A Factor Analysis of Behavioral Organization in Mice,” Zhurnal Vysshe? Nervno? Deiatenlnosti Imeni I P Pavlova, Vol. 42, No. 2, 1992, pp. 314-324.
 E. L. Mattiuz, G. D. Ponsler, R. J. Barbuch, P. G. Wood, J. H. Mullen, R. L. Shugert, Q. Li, W. J. Wheeler, F. Kuo, P. C. Conrad and J.-M. Sauer, “Disposition and Metabolic Fate of Atomoxetine Hydrochloride: Pharmacokinetics, Metabolism and Excretion in the Fischer 344 Rat and Beagle Dog,” Drug Metabolism and Disposition, Vol. 31, No. 1, 2003, pp. 88-97. doi:10.1124/dmd.31.1.88
 A. B. Fernando, D. Economidou, D. E. Theobald, M. F. Zou, A. H. Newman, M. Spoelder, D. Caprioli, M. Moreno, L. Hipólito, A. T. Aspinall, T. W. Robbins, J. W. Dalley, “Modulation of High Impulsivity and Attentional Performance in Rats By Selective Direct and Indirect Dopaminergic and Noradrenergic Receptor Agonists,” Psychopharmacology (Berl), Vol. 219, No. 2, 2012, pp. 341-52. doi:10.1007/s00213-011-2408-z
 C. G. de Jong, S. van de Voorde, H. Roeyers, R. Raymaekers, A. J. Allen, S. Knijff, H. Verhelst, A. H. Temmink, L. M. Smit, R. Rodriques-Pereira, D. Vandenberghe, W. van I, L. ter Schuren, M. Al Hakim, A. Amin, L. Vlasveld, J. Oosterlaan, and J. A. Sergeant, “Differential Effects of Atomoxetine on Executive Functioning and Lexical Decision in Attention-Deficit/Hyperactivity Disorder and Reading Disorder,” Journal of Child Adolescent Psychopharmacology, Vol. 19, No. 6, 2009, pp. 699-707.