Abstract
The Naples High- (NHE) and Low-Excitability (NLE) rat lines have been selected since 1976 on the basis of behavioral arousal to novelty (Làt-maze). Selective breeding has been conducted under continuous genetic pressure, with no brother-sister mating. The behavioral analyses presented here deal with (1) activity in environments of different complexity, i.e., holeboard and Làt maze; (2) maze learning in hexagonal tunnel, Olton, and Morris water mazes and; (3) two-way active avoidance and conditioned taste aversion tests. Morphometric analyses deal with central dopaminergic systems at their origin and target sites, as well as the density of dopamine transporter immunoreactivity. Molecular biology analyses are also presented, dealing with recent experiments on the prefrontal cortex (PFc), cloning and identifying differentially expressed genes using subtractive libraries and RNAase protection. The divergence between NLE and NHE rats varies as a function of the complexity level of the environment, with an impaired working and reference memory in both lines compared to random bred (NRB) controls. Moreover, data from the PFc of NHE rats show a hyperdopaminergic innervation, with overexpression of mRNA species involved in basal metabolism, and down-regulation of dopamine D1 receptors. Altogether, the evidence gathered so far supports a hyperfunctioning mesocorticolimbic system that makes NHE rats a useful tool for the study of hyperactivity and attention deficit, learning and memory disabilities, and drug abuse.
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REFERENCES
Alessandri, B., Battig, K., and Welzl, H. (1989). Effects of ketamine on tunnel maze and water maze performance in the rat. Behav. Neural. Biol. 52:194–212.
Aspide, R., Gironi, Carnevale, U. A., Sergeant, J. A., and Sadile, A. G. (1998). Non-selective attention and nitric oxide in putative animal models of attention-deficit hyperactivity disorder. Behav. Brain Res. 95:123–133.
Bjorklund, A., and Lindvall, O. (1984). Dopamine containing systems in the CNS. In Bjorklund, A. and Hokfelt, T. (eds), Handbook of Chemical Neuroanatomy, Elsevier, Amsterdam, pp. 55–122.
Burke, R. E., Cadet, J. L., Kent, J. D., Karanas, A. I., and Jackson-Lewis, V. (1990). An assessment of the validity of densitometric measures of striatal tyrosine hydroxylase-positive fibers: Relationship to apomorphine-induced rotations in 6-hydroxydopamine lesioned rats. J. Neurosci. Meth. 35:63–73.
Cerbone, A., Grimaldi, A., Lamberti, C., Manzi, G., and Sadile, A. G. (1985). Task and genotype-dependent associative and non associative behavioural modifications in the albino rat. Behav. Brain Res. 16:196.
Cerbone, A., Patacchioli, F. R., and Sadile, A. G. (1993a). A neurogenetic and morphogenetic approach to hippocampal functions based on individual differences and neurobehavioral covariations. Behav. Brain Res. 55:1–16.
Cerbone, A., Pellicano, M. P., and Sadile, A. G. (1993b). Evidence for and against the Naples High-and Low-Excitability rats as genetic model to study hippocampal functions. Neurosci. Biobehav. Rev. 17:295–304.
Chomczynski, P., and Sacchi, N. (1987). Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal. Biochem. 162:156–159.
Chozick, B. S. (1983). The behavioral effects of lesions of the hippocampus: A review. Int. J. Neurosci. 22:63–80.
Ciliax, B. J., Heilman, C., Demchyshyn, L. L., Pristupa, Z. B., Ince, E., Hersch, S. M., Niznik, H. B., and Levey, A. I. (1995). The dopamine transporter: Immunochemical characterization and localization in brain. J. Neurosci. 15:1714–1723.
Crusio, W. E. (1992). Quantitative genetics. In Goldowitz, D., Wahlsten, D., and Wimer, R. E. (eds), Techniques for the Genetic Analysis of Brain and Behavior, Elsevier Science Publishers B.V., Amsterdam pp. 231–250.
Diatchenko, L., Lau, Y.-F. C., Campbell, A. P., Chenchik, A., Moqadam, F., Huang, B., Lukyanov, S., Lukyanov, K., Gurskaya, N., Sverdlov, E. D., and Siebert, P. D. (1996). Suppression subtractive hybridization: A method for generating differentially regulated or tissue-specific cDNA probes and libraries. Proc. Natl. Acad. Sci. USA 93:6025–6030.
Durstewitz, D., Kelc, M., and Güntürkün, O. (1999). A neurocomputational theory of the dopaminergic modulation of working memory functions. J. Neurosci. 19:2807–2822.
Fallon, J. H., and Loughlin, S. E. (1982). Monoamine innervation of the forebrain: Collateralization. Brain Res. Bull. 9:295–307.
Finkelstein, D. I., Stanic, D., Parish, C. L., Tomas, D., Dickson, K., and Horne, M. K. (2000). Axonal sprouting following lesions of the rat substantia nigra. Neuroscience 97:99–112.
Foulkes, N. S., Borrelli, E., and Sassone, C. (1991). CREM gene: Use of alternative DNA-binding domains generates multiple antagonists of cAMP-induced transcription. Cell 64:739–749.
Fresiello, A., De Filippis, G., and Sadile, A. G. (1998). The behavioral profile of the Naples high-excitability and low-excitability rat lines in the Elevated Plus Maze. Soc. Neurosci. Abstr. 24:Part II, 1428.
Gallo, A., Gonzalez-Lima, F., and Sadile, A. (2002). Impaired metabolic capacity in the perirhinal and posterior parietal cortex lead to dissociation between attentional, motivational and spatial components of exploration in the Naples high excitability rat line. Behav. Brain Res. 130:133–140.
Garcia, F., Ervin, F., Yorke, C., and Koelling, R. (1967). Conditioning with delayed vitamine injections. Science 155:716–718.
Gironi Carnevale, U. A., Vitullo, E., and Sadile, A. G. (1990). Posttrial NMDA receptor allosteric blockade differentially influences habituation of behavioral responses to novelty in the rat. Behav. Brain Res. 39:187–195.
Giros, B., Jaber, M., Jones, S. R., Wightman, R. M., and Caron, M. G. (1996). Hyperlocomotion and indifference to cocaine and amphetamine in mice lacking the dopamine transporter. Nature 379:606–612.
Gray, J. A., and McNaughton, N. (1983). Comparison between the behavioral effects of septal and hippocampal lesions: A review. Neurosci. Biobehav. Rev. 7:119–188.
Hegmann, J. P., and Possidente, B. (1981). Estimating genetic correlations from inbred strains. Behav. Genet. 11:103–114.
Jones, S. R., Gainetdinov, R. R., Jaber, M., Giros, B., Wightman, R. M., and Caron, M. G. (1998). Profound neuronal plasticity in response to inactivation of the dopamine transporter. Proc. Natl. Acad. Sci. USA 95:4029–4034.
Kalivas, P. W., and Nakamura, M. (1999). Neural systems for behavioral activation and reward. Curr. Opin. Neurobiol. 9:223–227.
Kandel, E. R., Schwartz, J. H., and Jessell, T. M. (2000). Principles of Neural Science. Elsevier, Amsterdam.
Morris, R. G., Anderson, E., Lynch, G. S., and Baudry, M. (1986). Selective impairment of learning and blockade of long-term potentiation by an N-methyl-D-aspartate receptor antagonist, AP5 Nature 19774–776.
Murphy, B. L., Arnsten, A. F., Goldman, R., and Roth, R. H. (1996). Increased dopamine turnover in the prefrontal cortex impairs spatial working memory performance in rats and monkeys. Proc. Natl. Acad. Sci. USA 93:1325–1329.
Ohl, F., Holsboer, F., and Landgraf, R. (2001). The modified hole board as a differential screen for behavior in rodents. Behav. Res. Methods Instrum. Comput. 33:392–397.
Olton, D. S., Walker, J. A., and Gage, F. H. (1978). Hippocampal connections and spatial discrimination. Brain Res. 139:295–308.
Pellicano, M. P., Siciliano, F., and Sadile, A. G. (1993). NMDA receptors modulate behavioral plasticity as assessed by dose and genotype-dependent differential effects of post-trial MK-801 and CPP on long-term habituation to spatial novelty in rats. Physiol. Behav. 54:563–568.
Plomin, R., and McClearn, G. E. (1993). Quantitative trait loci (QTL) analyses and alcohol-related behaviors. Behav. Genet. 23:197–211.
Sadile, A., Cerbone, A., Lamberti, C., and Cioffi, L. A. (1984). The Naples High (NHE) and Low Excitable (NLE) rat strains: A progressive Report. Behav. Brain Res. 12:228–229.
Sadile, A. G. (1993). What can genetic models tell us about behavioral plasticity? Rev. Neurosci. 4:287–303.
Sadile, A. G. (1996). Long-term habituation of theta-related activity components of albino rats in the Làt-maze. In Sanberg, P. R., Ossenkopp, K. P., and Kavaliers, M. (eds), Motor Activity and Movement Disorders: Measurement and Analysis, Humana Press, New York, pp. 1–54.
Sadile, A. G., Cerbone, A., Grimaldi, A., and Manzi, G., and Cioffi, L. A. (1986). Postnatal brain growth and behavior: Evaluation of environmental factors. Bibl. Nutr. Diet. 38:194–205.
Sadile, A. G., Cerbone, A., Manzi, G., and Grimaldi, A. (1983). Bidirectional asymmetrical selection for behavioral arousal to novel environment: Naples High (NHE) and Low (NLE) Excitable rat strains. Soc. Neurosci. Abstr. 9:643.
Sadile, A. G., Gironi Carnevale, U. A., Vitullo, E., Cioffi, L. A., Welzl, H., and Bättig, K. (1988). Maze learning of the Naples High-and Low-Excitability rat lines. Adv. Biosci. 70:177–180.
Sadile, A. G., Lamberti, C., Siegfried, B., and Welzl, H. (1993). Circadian activity level, nociceptive thresholds, nigrostriatal and mesolimbic dopaminergic activity in the Naples High-and Low-Excitability rat lines. Behav. Brain Res. 55:17–27.
Sambrook, J., Fritsch, E. F., and Maniatis, T. (1997). Molecular Cloning. A Laboratory Manual, Nolan, C. (ed), Cold Spring Harbor Laboratory Press, NY.
Sawaguchi, T., Matsumura, M., and Kubota, K. (1990). Cathecolaminergic effects on neuronal activity related to a delayed response task in monkey prefrontal cortex. J. Neurophysiol. 63: 1385–1400.
Solanto, M. V. (1998). Neuropsychopharmacological mechanisms of stimulant drug action in attention-deficit hypractivity disorder: A review and integration. Behav. Brain Res. 94:127–152.
Swanson, J., Castellanos, F. X., Murias, M., La Hoste, G., and Kennedy, J. (1998). Cognitive neuroscience of attention deficit hyperactivity disorder and hyperkinetic disorder. Curr. Opin. Neurobiol. 8:263–271.
Vallone, D., Battista, S., Pierantoni, G. M., Fedele, M., Casalino, L., Santoro, M., Viglietto, G., Fusco, A., and Verde, P. (1997). Neoplastic transformation of rat thyroid cells requires the junB and fra-1 gene induction which is dependent on the HMGI-C gene product. EMBO J. 16:5310–5321.
Vallone, D., Picetti, R., and Borrelli, E. (2000). Structure and function of dopamine receptors. Neurosci. Biobehav. Rev. 24:125–132.
Van Eden, C. G., Hoorneman, E. M., Buijs, R. M., Matthijssen, M. A., Geffard, M., and Uylings, H. B. (1987). Immunocytochemical localization of dopamine in the prefrontal cortex of the rat at the light and electron microscopical level. Neuroscience 22:849–862.
Van Eden C. G., and Uylings, H. B. (1985). Cytoarchitectonic development of the prefrontal cortex in the rat. J. Comp. Neurol. 241:253–267.
Viggiano, D., Grammatikopoulos, G., and Sadile, A. (2002). A morphometric evidence for a hyperfunctioning mesolimbic system in an animal model of ADHD. Behav. Brain Res. 130:181–189.
Viggiano, D., and Sadile, A. G. (2000). Hypertrophic A10 dopamine neurons in a rat model of attention-deficit hyperactivity disorder (ADHD). Neuroreport 11:3677–3680.
Whishaw, I. Q., and Vanderwolf, C. H. (1973). Hippocampal EEG and behavior: Changes in amplitude and frequency of RSA (theta rhythm) associated with spontaneous and learned movement patterns in rats and cats. Behav. Biol. 8:461–484.
Williams, G. V., and Goldman, R. (1995). Modulation of memory fields by dopamine D1 receptors in prefrontal cortex. Nature 376:572–575.
Zahm, D. S. (2000). An integrative neuroanatomical perspective on some subcortical substrates of adaptive responding with emphasis on the nucleus accumbes. Neurosci. Biobehav. Rev. 24:85–106.
Zahrt, J., Taylor, J. R., Mathew, R. G., and Arnsten, A. F. (1997). Supranormal stimulation of D1 dopamine receptors in the rodent prefrontal cortex impairs spatial working memory performance. J. Neurosci. 17:8528–8535.
Zhuang, X., Oosting, R. S., Jones, R. S., Gainetdinov, R. R., Miller, G. W., Caron, M. G., and Hen, R. (2001). Hyperactivity and impaired response habituation in hyperdopaminergic mice. Proc. Natl. Acad. Sci. USA, 98:1982–1987.
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Viggiano, D., Vallone, D., Welzl, H. et al. The Naples High- and Low-Excitability Rats: Selective Breeding, Behavioral Profile, Morphometry, and Molecular Biology of the Mesocortical Dopamine System. Behav Genet 32, 315–333 (2002). https://doi.org/10.1023/A:1020210221156
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DOI: https://doi.org/10.1023/A:1020210221156