Skip to main content

Apomorphine Susceptibility and Animal Models for Psychopathology: Genes and Environment

Behavior Genetics volume 32, pages 349–361 (2002)Cite this article

Abstract

Many years ago we found a bimodal distribution of a number of different behaviors in our regular outbred Wistar stock. This was observed in the response to novelty, the response in a resident-intruder test as well as in the stereotypy response to the dopamine agonist apomorphine. On the basis of that, we decided to selectively breed these animals, which resulted in the the APO-SUS and APO-UNSUS lines. The APO-SUS rats show a strong, stereotyped gnawing response, whereas APO-UNSUS show only a weak gnawing response. Follow-up studies have shown that the phenotypical expression of these rats depend on genetic and early and late environmental factors. Because these rats were not selected on the basis of a specific behavioral trait, but rather on the basis of a difference in susceptibility for a specific neurotransmitter, it is not surprising that these animals show major differences in the neurochemical state of the central nervous system. In fact, in many respects they represent mirror images of each other. Moreover, these animals show clear differences in their endocrine and immunological systems. APO-SUS rats can be characterized as having a hyper-reactive hypothalamus-pituitary-adrenal axis, and a dominance of the TH2 system. Apart from discussing the main differences between APO-SUS and APO-UNSUS rats, the review specifically focuses on the former as a potential model for schizophrenia. We have been able to show that APO-SUS rats indeed share a large number of behavioral, neurochemical, endocrinological, and immunological similarities with patients suffering from schizophrenia. Because schizophrenia is also likely to result from an interaction between genetic and early stressful life events, the APO-SUS rat might represent a promising animal model for studying this severe mental disorder.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

39,95 €

Price includes VAT (Finland)

REFERENCES

  • Baruch, I., Hemsley, D. R., and Gray, J. A. (1988). Differential performance of acute and chronic schizophrenics in a latent inhibition task. J. Nerv. Ment. Dis. 176:598–606.

    PubMed  Google Scholar 

  • Benus, R. F., Bohus, B., Koolhaas, J. M., and van Oortmerssen, G. A. (1991). Behavioural differences between artificially selected aggressive and non-aggressive mice: Response to apomorphine. Behav. Brain Res. 43:203–208.

    PubMed  Google Scholar 

  • Bolhuis, J. E., Schouten, W. G. P., de Jong, I. C., Schrama, J. W., Cools, A. R., and Wiegant, V. M. (2000). Response to apomorphine of pigs with different coping characteristics. Psychopharmacology 152:24–30.

    PubMed  Google Scholar 

  • Braff, D., Stone, C., Callaway, E., Geyer, M. A., Glick, I. D., and Bali, L. (1978). Prestimulus effects of human startle reflex in normals and schizophrenics. Psychophysiology 15:339–343.

    PubMed  Google Scholar 

  • Breivik, T., Sluyter, F., Hof, M., and Cools, A. R. (2000). Differential susceptibility to periodontitis in genetically selected Wistar rat lines that differ in their behavioral and endocrinological response to stressors. Behav. Genet. 30:123 –130.

    Google Scholar 

  • Breivik, T., Thrane, P. S., Murison, R., and Gjermo, P. (1996). Emotional stress eff3ects on immunity, gingivitis and periodontitis. Eur. J. Oral Sci. 104:327–334.

    PubMed  Google Scholar 

  • Cabib, S., Oliverio, A., Ventura, R., Luchesse, F., and Puglisi Allegra, S. (1997). Brain dopamine receptor plasticity: Testing a diathesis-stress hypothesis in an animal model. Psychopharmacology 132:153–160.

    PubMed  Google Scholar 

  • Chiu, P., Rajakumar, G., Chiu, S., Kwan, C. Y., and Mishra, R. K. (1984). Differential changes in central serotonin and dopamine receptors in spontaneous hypertensive rats. Prog. Neuropsychopharmacol. Biol. Psychiatry 8:665–668.

    PubMed  Google Scholar 

  • Connell, P. (1958). Amphetamine Psychosis. Oxford University Press, London.

    Google Scholar 

  • Cools, A. R., Brachten, R., Heeren, D., Willemen, A., and Ellenbroek B. (1990). Search after neurobiological profile of individualspecific features of Wistar rats. Brain Res. Bull. 24:49–69.

    PubMed  Google Scholar 

  • Cools, A. R., Dierx, J., Coenders, C., Heeren, D., Ried, S., Jenks, B. G., and Ellenbroek, B. (1993a). Apomorphine-susceptible and apomorphine-unsusceptible Wistar rats differ in novelty-induced changes in hippocampal dynorphin B expression and two-way active avoidance: A new key in the search for the role of the hippocampalaccumbens axis. Behav. Brain Res. 55:213–221.

    PubMed  Google Scholar 

  • Cools, A. R., and Ellenbroek, B. A. (2002). Animal models of personality. In D'Haenen, H., den Boer, J. A., Westenberg, H., and Willner P. (eds.), Textbook of Biological Psychiatry, John Wiley & Sons, Chichester, pp. 1333–1344.

    Google Scholar 

  • Cools, A. R., Ellenbroek, B. A., Gingras, M. A., Engbersen, A., and Heeren, D. (1997). Differences in vulnerability and susceptibility to dexamphetamine in Nijmegen high and low responders to novelty: A dose-effect analysis of spatio-temporal programming of behaviour. Psychopharmacology Berl. 132:181–187.

    PubMed  Google Scholar 

  • Cools, A. R., and Gingras, M. A. (1998). Nijmegen high and low responders to novelty: A new tool in the search after the neurobiology of drug abuse liability. Pharmacol. Biochem. Behav. 60:151–159.

    PubMed  Google Scholar 

  • Cools, A. R., Rots, N. Y., Ellenbroek, B., and de Kloet, E. (1993b). Bimodal shape of individual variation in behavior of Wistar rats: The overall outcome of a fundamentally different make-up and reactivity of the brain, the endocrinological and the immunological system. Neuropsychobiology 28:100–105.

    PubMed  Google Scholar 

  • Costall, B., and Naylor, R. (1973). The role of telencephalic dopaminergic systems in the mediation of apomorphine stereotyped behavior. Eur. J. Pharmacol. 24:8–24.

    PubMed  Google Scholar 

  • Crusio, W. E., Schwegler, H., and van Abeelen, J. H. F. (1989). Behavioral responses to novelty and structural variation of the hippocampus in mice. I. Quantitative-genetic analysis of behaviour in the open field. Behav. Brain Res. 32:75–80.

    PubMed  Google Scholar 

  • Daynes, R. A., Araneo, B. A., Dowell, T. A., Huaang, K., and Dudley, D. (1990). Regulation of murine lymphokine production in vivo. III. The lymphoid tissue microenvironment exerts regulatory influences over T helper cell function. J. Exp. Med. 171:979–996.

    PubMed  Google Scholar 

  • de Bruin, N. M. W. J., van Luijtelaar, E. L. J. M., Cools, A. R., and Ellenbroek B. A. (2001). Dopamine characteristics in rat genotypes with distinct susceptibility to epileptic activity: Apomorphine-induced stereotyped gnawing and novelty/amphetamineinduced locomotor stimulation. Behav. Pharmacol. 12:517–525.

    PubMed  Google Scholar 

  • Deleplanque B., Neveu, P. J., Vitiello, S., and LeMoal, M. (1992). Early effects of unilateral lesions of substantia nigra on immune Reactivity. Neurosci. Lett. 135:205–209.

    PubMed  Google Scholar 

  • Driscoll, P., Escorihuela, R. M., Fernandez-Teruel, A., Giorgi, O., Schwegler, H., Steimer, T., Wiersma, A., Corda, M. G., Flint, J., Koolhaas, J. M., Langhans, W., Schulz, P. E., Siegel, J., and Tobena, A. (1998). Genetic selection and differential stress responses: The Roman Lines/strains of rats. Ann. N.Y. Acad. Sci. 851:501–510.

    PubMed  Google Scholar 

  • Driscoll, P., Lieblich, I., and Cohen, E. (1986). Amphetamineinduced stereotypic responses in Roman high-and Roman lowavoidance rats. Pharmacol. Biochem. Behav. 24:1329–1332.

    PubMed  Google Scholar 

  • Ellenbroek, B. A., and Cools, A. R. (1993). Stereotyped behaviour. In van Haaren, F. C. (ed.), Methods in Behavioral Pharmacology, Elsevier, Amsterdan, pp. 519–538.

    Google Scholar 

  • Ellenbroek, B. A., and Cools, A. R. (2000). Animal models for the negative symptoms of schizophrenia. Behav. Pharmacol. 11: 223–233.

    PubMed  Google Scholar 

  • Ellenbroek, B. A., and Cools, A. R. (2002). Animal models for schizophrenia, In D'Haenen, H., den Boer, J. A., Westenberg, H., and Willner P. (eds.), Textbook of Biological Psychiatry, John Wiley & Sons, Chichester, pp. 567–580.

    Google Scholar 

  • Ellenbroek, B. A., Geyer, M. A., and Cools, A. R. (1995). The behavior of APO-SUS rats in animal models with construct validity for schizophrenia. J. Neurosci. 15:7604–7611.

    PubMed  Google Scholar 

  • Ellenbroek, B. A., Sluyter, F., and Cools, A. R. (2000). The role of genetic and early environmental factors in determining apomorphine susceptibility. Psychopharmacology 148:124–131.

    PubMed  Google Scholar 

  • Essman, W. D., McGonigle, P., and Lucki, I. (1992). Variations in the behavioural responses produced by apomorphine in different strains of rats. Soc. Neurosci. Abstr. 18:877.

    Google Scholar 

  • Feldman, S., and Conforti, N. (1980). Participation of the dorsal hippocampus in the glucocorticoid feedback effect on adrenocortical activity. Neuroendocrinology 30:52–55.

    PubMed  Google Scholar 

  • Geyer, M. A., Krebs-Thomson, K., Braff, D. L., and Swerdlow, N. R. (2001). Pharmacological studies of prepulse inhibition models of sensorimotor gating deficits in schizophrenic patients: A decade in review. Psychopharmacology 156:117–154.

    PubMed  Google Scholar 

  • Gingras, M. A., and Cools, A. R. (1996). Analysis of the biphasic locomotor response to ethanol in high and low responders to novelty: A study in Nijmegen Wistar rats. Psychopharmacology 125:258–264.

    PubMed  Google Scholar 

  • Harnack, E. (1874). Ñber die Wirkungen des Apomorphins am Saugetier und am Frosch. Arch. Exp. Pathol. Pharmacol. 2:254–306.

    Google Scholar 

  • Helmeste, D. M. (1983). Spontaneous and apomorphine-induced locomotor changes parallel dopamine receptor differences in two rats strains. Pharmacol. Biochem. Behav. 19:153–155.

    PubMed  Google Scholar 

  • Herman, J. P., Schafer, K. H., Young, E. A., Thompson, R., Douglass, J., Akil, H., and Watson, S. J. (1989). Evidence for a hippocampal regulation of neuroendocrine neurons of the hypothalamopituitary-adrenocortical axis. J. Neurosci. 9:3072–3082.

    PubMed  Google Scholar 

  • Hooks, M. S., Jones, G. H., Neill, D. B., and Justice, J. B. J. (1991). Individual differences in amphetamine sensitization: Dosedependent effects. Pharmacol. Biochem. Behav. 41:203–210.

    Google Scholar 

  • Kavelaars, A., Heijnen, C. J., Ellenbroek, B., van Loveren, H., and Cools, A. (1997). Apomorphine-susceptible and apomorphineunsusceptible Wistar rats differ in their susceptibility to inflammatory and infectious diseases: A study on rats with group-specific differences in structure and reactivity of hypothalamic-pituitary-adrenal axis. J. Neurosci. 17:2580–2584.

    PubMed  Google Scholar 

  • Kelley, K. W., and Dantzer, R. (1991). Growth hormone and prolactin as natural antagonists of glucocorticoids in immuneregulation. In Plotnikoff, N., Murgo, A., Faith, R., and Wybran, J. (eds.), Stress and Immunity,CRC Press, Boca Raton, pp. 433–452.

    Google Scholar 

  • Kinney, G. G., Wilkinson, L. O., Saywell, K. L., and Tricklebank, M. D. (1999). Rat strain differences in the ability to disrupt sensorimotor gating are limited to the dopaminergic system, specific to prepulse inhibition, and unrelated to changes in startle amplitude or nucleus accumbens dopamine receptor sensitivity. J. Neurosci. 19:5644–5653.

    PubMed  Google Scholar 

  • Krauchi, K., Wirz-Justice, A., Willener, R., Campbell, I. C., and Feer, H. (1983). Spontaneous hypertensive rats: Behavioral and corticosterone response depend on circadian phase. Physiol. Behav. 30:35–40.

    PubMed  Google Scholar 

  • Lammers, C.-H., Garcia-Borreguero, D., Schmider, J., Gotthardt, U., Dettling, M., Holsboer, F., and Heuser, I. J. E. (1995). Combined dexamethasone/corticotropin-releasing hormone test in patients with schizophrenia and in normal controls II. Biol. Psychiatry 38:803–807.

    PubMed  Google Scholar 

  • Laruelle, M. (2000). The role of endogenous sensitization in the pathophysiology of schizophrenia: Implications from recent brain imaging studies. Brain Res. Rev. 31:371–384.

    PubMed  Google Scholar 

  • Lieberman, J. A., Kane, J. M., and Alvir, J. (1987). Provocative tests with psychostimulant drugs in schizophrenia. Psychopharmacology 91:415–533.

    PubMed  Google Scholar 

  • Liebsch, G., Montkowski, A., Holsboer, F., and Landgraf, R. (1998). Behavioural profiles of two Wistar rat lines selectively bred for high or low anxiety-related behaviour. Behav. Brain Res. 94:301–310.

    PubMed  Google Scholar 

  • Ljungberg, T., and Ungerstedt, U. (1978). A new method for simultaneous registration of 8 behavioral parameters related to monoamine neurotransmission. Pharmacol. Biochem. Behav. 8:483–489.

    PubMed  Google Scholar 

  • Mortensen, P. B. (1994). The occurrence of cancer in first admitted schizophrenic patients. Schizophr. Res. 12:185–194.

    PubMed  Google Scholar 

  • Moynihan, J. A., Karp, J. D., Cohen, N., and Crocke, R. (1994). Alterations in IL-4 and antibody production following pheromone exposure: Role of glucocorticoids. J. Neuroimmunol. 54:51–58.

    PubMed  Google Scholar 

  • Mulders, W. H., Meek, J., Schmidt, E. D., Hafmans, T. G., and Cools, A. R. (1995). The hypothalamic paraventricular nucleus in two types of Wistar rats with different stress responses. II. Differential Fos-expression. Brain Res. 689:61–70.

    PubMed  Google Scholar 

  • Muller, N., Riedel, M., Ackenheil, M., and Schwarz, M. J. (1999). The role of immune function in schizophrenia: An overview. Eur. Arch. Psychiatry Clin. Neurosci. 249(Suppl. 4):62–68.

    Google Scholar 

  • Muller, S. F., Modell, S., Ackenheil, M., Brachner, A., and Kurtz, G. (1998). Elevated response of growth hormone to graded doses of apomorphine in schizophrenic patients. J. Psychiatr. Res. 32:265–271.

    PubMed  Google Scholar 

  • Munck, A., and Guyre, P. M. (1990). Glucocorticoids and the immune system. In Ader, R., Felten, D. L., and Cohen, N. (eds.), Psychoneuroimmunology,Elsevier, Amsterdam, pp. 447–474.

    Google Scholar 

  • Nusslein, H. G., Weber, G., and Kalden, J. R. (1994). Synthetic glucocorticoids potentiate IgE synthesis: Influence of steroid and non-steroid hormones on human in vitro IgE secretion. Allergy 49:370.

    Google Scholar 

  • Papp, M., Willner, P., and Muscat, R. (1991). An animal model of anhedonia: attenuation of sucrose consumption and place preference conditioning by chronic unpredictable mild stress. Psychopharmacology 104:255–259.

    PubMed  Google Scholar 

  • Petitto, J. M., McCarthy, D. B., Rinker, C. M., Huang, Z., and Getty, T. (1997). Modulation of behavioral and neurochemical measures of forebrain dopamine function in mice by speciesspecific interleukin-2. J. Neuroimmunol. 73:183–190.

    PubMed  Google Scholar 

  • Piazza, P. V., Deminiere, J. M., Maccari, S., Mormede, P., LeMoal, M., and Simon, H. (1990). Individual reactivity to novelty predicts probability of amphetamine self-administration. Behav. Pharmacol. 1:339–345.

    PubMed  Google Scholar 

  • Randrup, A., and Munkvad, I. (1966). Stereotyped activities produced by amphetamine in several animal species and man. Psychopharmacology 11:300–310.

    Google Scholar 

  • Ricci, A., Mariotta, S., Greco, S., and Bisetti, A. (1997). Expression of dopamine receptors in immune organs and circulating immune cells. Clin. Exp. Hypertens. 19:59–71.

    PubMed  Google Scholar 

  • Rigdon, G. C. (1990). Differential effects of apomorphine on prepulse inhibition of acoustic startle reflex in two rat strains. Psychopharmacology 102:419–421.

    PubMed  Google Scholar 

  • Riksen, N. P., Ellenbroek, B. A., Cools, A. R., Siero, H. L., Rongen, G. A., Smits, B. W., Russel, F. G. M., and Smits, P. (2002). Stress susceptibility as a determinant of the release of endothelium derived relaxing and contracting factors in rat mesenteric arteries. J. Cardiovasc. Pharmacol. in press.

  • Rots, N. Y., Cools, A. R., Berod, A., Voorn, P., Rostene, W., and de Kloet, E. (1996a). Rats bred for enhanced apomorphine sus-ceptibility have elevated tyrosine hydroxylase mRNA and dopamine D2-receptor binding sites in nigrostriatal and tuberoinfundibular dopamine systems. Brain Res. 710:189–196.

    PubMed  Google Scholar 

  • Rots, N. Y., Cools, A. R., De Jong, J., and de Kloet, E. (1995). Corticosteroid feedback resistance in rats genetically selected for increased dopamine responsiveness [published erratum appears in J. Neuroendocrinol. (1995) 7:280]. J. Neuroendocrinol. 7: 153–161.

    PubMed  Google Scholar 

  • Rots, N. Y., Cools, A. R., Oitzl, M. S., De Jong, J., Sutanto, W., and de Kloet, E. (1996b). Divergent prolactin and pituitary-adrenal activity in rats selectively bred for different dopamine responsiveness. Endocrinology 137:1678–1686.

    PubMed  Google Scholar 

  • Rots, N. Y., Workel, J., Oitzl, M. S., Berod, A., Rostene, W., Cools, A. R., and de Kloet, E. R. (1996c). Development of divergence in dopamine responsiveness in genetically selected rat lines is preceded by changes in pituitary-adrenal activity. Dev. Brain Res. 92:164–171.

    Google Scholar 

  • Saigusa, T., Tuinstra, T., Koshikawa, N., and Cools, A. R. (1999). High and low responders to novelty: Effects of a catecholamine synthesis inhibitor on novelty-induced changes in behaviour and release of accumbal dopamine. Neuroscience 88:1153–1163.

    PubMed  Google Scholar 

  • Sapolsky, R. M., Zola-Morgan, S., and Squire, L. R. (1991). Inhibition of glucocorticoid secretion by the hippocampal formation in the primate. J. Neurosci. 11:3695–3704.

    PubMed  Google Scholar 

  • Schopke, R., Wolter, D. P., Lipp, H. P., and Leisinger-Trigona, M. C. (1991). Swimming navigation and structural variations on the infrapyramidal mossy fibers in the hippocampus of the mouse. Hippocampus 1:315–328.

    PubMed  Google Scholar 

  • Schouten, W. G. P., and Wiegant, V. M. (1997). Individual responses to acute and chronic stress in pigs. Acta Physiol. Scand. 161(Suppl 640):88–91.

    Google Scholar 

  • Schwegler, H., and Lipp, H. P. (1983). Hereditary covariations of neuronal circuitry and behavior: Correlations between the proportions of hippocampal synaptic terminal fields in the regio inferior and two-way active avoidance in mice and rats. Behav. Brain Res. 7:1–38.

    PubMed  Google Scholar 

  • Smits, B. W., Siero, H. L., Ellenbroek, B. A., Riksen, N. P., Cools, A. R., Rongen, G. A., Russel, F. G. M., and Smits, P. (2002). Stress susceptibility as a determinant of the response to adrenergic stimuli in mesenteric resistance arteries of the rat. J. Cardiovasc. Pharmacol. in press.

  • Spooren, W. P. J. M., Lubbers, L., Jenks, B. G., and Cools, A. R. (1999). Variation in hippocampal dynorphin B-immunoreactive mossy fiber terminal fields of apomporphine-(un)-susceptible rats. J. Chem. Neuroanat. 17:59–64.

    PubMed  Google Scholar 

  • Swerdlow, N. R., Martinez, Z. A., Hanlon, F. M., Platten, A., Farid, M., Auerbach, P., Braff, D. L., and Geyer, M. A. (2000). Toward understanding the biology of a complex phenotype: Rat strain and substrain differences in the sensorimotor gatingdisruptive effects of dopamine agonists. J. Neurosci. 20:4325–4336.

    PubMed  Google Scholar 

  • Tang, A. H., and Himes, C. S. (1995). Apomorphine produced more yawning in Sprague-Dawley rats than in F344 rats: A pharmacological study. Eur. J. Pharmacol. 284:13–18.

    PubMed  Google Scholar 

  • Teunis, M. A. T., Kavelaars, A., Voest, E., Bakker, J. M., Ellenbroek, B. A., Cools, A. R., and Heijnen, C. J. (2002). Reduced tumor growth, experimental metastasis formation, and angiogenesis in rats with a hyperreactive dopaminergic dopaminergic system. FASEB J (in press).

  • Tuinstra, T., Verheij, M., Willemen, A., Iking, J., Heeren, D. J., and Cools, A. R. (2000). Retrieval of spatial information in Nijmegen high and low responders: Involvement of beta-adrenergic mechanisms in the nucleus accumbens. Behav. Neurosci. 114:1088–1095.

    PubMed  Google Scholar 

  • van Abeelen, J. H. F. (1989). Genetic control of hippocampal cholinergic and dynorphinergic mechanisms regulating noveltyinduced exploratory behavior in house mice. Experientia 45:839–845.

    PubMed  Google Scholar 

  • van de Langerijt, A. G., van Lent, P. L., Hermus, A. R., Sweep, C. G., Cools, A. R., and van den Berg, W. B. (1994). Susceptibility to adjuvant arthritis: Relative importance of adrenal activity and bacterial flora. Clin. Exp. Immunol. 97:33–38.

    PubMed  Google Scholar 

  • van den Buuse, M., and de Jong, W. (1989). Differential effects of dopaminergic drugs in open-field behavior of spontaneously hypertensive rats and normotensive Wistar-Kyoto rats. J. Pharmacol. Exp. Ther. 248:1189–1196.

    PubMed  Google Scholar 

  • van Oortmerssen, G. A., and Bakker, T. C. M. (1981). Artificial selection for short and long attack latencies in wild Mus domesticus. Behav. Genet. 11:115–126.

    Google Scholar 

  • Vaughan, C. E., van den Buuse, M., and Roland, B. L. (2000). Brain dopamine D2 receptor mRNA levels are elevated in young spontaneously hypertensive rats. Neurosci. Res. 34: 199–205.

    Google Scholar 

  • Verbeek, M. E. M., Drent, P. J., and Wiepkema, P. R. (1994). Consistent individual differences in early exploratory behaviour of male great tits. Anim. Behav. 48:1113–1121.

    Google Scholar 

  • Vinogradov, S., Gottesman, I. I., Moises, H. W., and Nichol, S. (1991). Negative association between schizophrenia and rheumatoid arthritis. Schizophr. Bull. 17:669–678.

    PubMed  Google Scholar 

  • Walker, C. D., Rivest, R. W., Meaney, M. J., and Aubert, M. L. (1989). Differential activation of the pituitary-adrenocortical axis after stress in the rat: Use of two genetically selected lines (Roman low-and high-avoidance rats) as a model. J. Endocrinol. 123:477–485.

    PubMed  Google Scholar 

  • Walker, E. F., and Diforio, D. (1997). Schizophrenia: A neural diathesis-stress model. Psychol. Rev. 104:667–685.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Psychoneuropharmacology, P.O. Box 9101, 6500 HB, Nijmegen, the, Netherlands

    Bart A. Ellenbroek & Alexander R. Cools

Authors
  1. Bart A. Ellenbroek
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alexander R. Cools
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Bart A. Ellenbroek.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Ellenbroek, B.A., Cools, A.R. Apomorphine Susceptibility and Animal Models for Psychopathology: Genes and Environment. Behav Genet 32, 349–361 (2002). https://doi.org/10.1023/A:1020214322065

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1020214322065

  • APO-SUS
  • APO-UNSUS
  • apomorphine
  • dopamine
  • schizophrenia
  • stress
  • Wistar