Abstract
We describe an animal model of long-term depression based on active immunization of albino rats against BSA-conjugated inhibitor of monoamine oxidase, antidepressant, pargyline. Immunization resulted in anti-pargyline antibody formation and significant activation of monoamine oxidase A in brain. Immunized rats demonstrated potent decrease of motor, orientation and exploratory activity, increase of the immobility time (“despair”) in Porsolt test, as well as notable signs of fear and anxiety in elevated plus maze. The cognitive processes were not significantly affected: the speed of learning with negative and positive reinforcement was not diminished. Complex effect on craving for alcohol (long-term suppression after short-term increase) was also demonstrated. The long-term (more than 45 days) depression achieved in this model makes it potentially important tool for testing new antidepressant pharmaceuticals.
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REFERENCES
Carelli, C., Andibert F., Gaillard, J., and Chedid, L. 1982. Immunological castration of male by a totally synthetic vaccine administered in saline. Proc. Natl. Acad. Sci. USA. 79:5392-5395.
Faris, P. L., McLaughlin, C. L., Baile, C. A., Olney, J. W., and Komisaruk, B. R. 1984. Morphine analgesia potentiated but tolerance not affected by active immunization against cholecystokinin. Science, 226:1215-1217.
Ashmarin, I. P., Danilova, R. A., Mashkovskii, M. D., Mel'nic, E. I., Obukhova, M. F., Sagimbaeva, Sh. K., and Tsirenina, M. L. 1990. Active immunization against bioregulators: behavioural and catecholamine changes in albino rats immunized against sydnophen. Biomed. Sci. 1:95-98.
Pshezhetsky, A. V., Danilova, R. A., Fedorova, I. M., Pervushina, S. V., Obukhova, M. F., Svedas, V. K., and Ashmarin, I. P. 1993. Influence of the immunization against heterologous alcohol dehydrogenase on liver alcohol dehydrogenase isozymes and alcohol abuse of rats. Eur. J. Biochem. 212:757-761.
Danilova, R. A., and Ashmarin, I. P. 1994. The inverse immuno-regulation of behavior and the problem of the existence of regulatory autoantibodies. Uspechi Physiol. Nauk. 25:3-23.
Vetrile, L. A., Krupina, N. A., Basharova, L. A., Kryzhanovsky, G. N., Evseev, V. A., Orlova, J. N., and Jordanskaya, T. E. 1997. The model of depression syndrome by MPTP and autoantibodies to serotonine and dophamine. J. Vish. Nervn. Dejat. 47:731-738.
Ashmarin, I. P., Buzinova, E., Vinogradova, M., Potier, M., and Pshezhetsky, A. 1997. Learning disability in rats induced by the immunosuppression of cathepsin A in blood plasma. Neurosci. Res. Comm. 21:153-162.
Meeker, M. L., Meeker, R. B., and Hayward, J. N. 1987. Accumulation of circulating endogenous and exogenous immunoglobulins by hypothalamic magnocellular neurones. Brain Res. 423:45-55.
Reiber, H., Kitze, B., Link, M., and Wagner, R. 1988. Cellular immune reactions and blood cerebrospinal fluid barier dysfunction in guinea pigs. Neurochem. Res. 13:463-466.
Podulso, J. F., Curran, G. L., and Berg, C. T. 1994. Macromolecular permeability across the blood-nerve and blood-brain barriers. Proc. Natl. Acad. Sci. USA 91:5705-5709.
Ashmarin, I. P., and Gomazkov, O. A. 1992. Active immunization against neurotransmitters and neuromodulators as a means of long-term correction of physiological functions. Sov. Sci. Rev. F. Physiol. Gen. Biol. 5:1-37.
Sara, S. J., Devauges, V., and Biegon, A. 1993. Maudsley rat strains, selected for differences in emotional responses, differ in behavioral response to clonidine and in [125I]-clonidine binding in the locus coeruleus Behav. Brain Res. 57:101-104.
Pakkel, V. A., and Kirkel, A. Z. 1985. The modified radiometric method of aminooxidase activity determination. Voprosy Meditzin. Himii. 31:122-125.
Porsolt, R. D., Anton, G., Blavet, N., and Jalfre, M. 1978. Behavioural dispare in rats: a new model sensitive to antidepressant drugs. Europ. J. Pharmacol. 47:379-384.
Pellow, S., Chopin, P., Files, S. E., and Briley, M. 1985. Validation of open:closed arm entries in an elevated plus-maze as a measure of anxiety in the rat. J.Neurosci.Meth. 14:149-167.
Danilova, R. A., Obukhova, M. F., Sagimbaeva, Sh. K., Mashkovskii, M. D., and Ashmarin, I. P. 1989. The immunocorrection of physiological status of albino rats by conjugates of sydnophen with BSA. Biolog. Nauki. 3:63-69.
Burov, Yu. V., and Vedernikova, N. N. 1985. In: Neurochemistry and pharmacology of alcoholism. Meditsina, Moscow.
Panova, N. G., Zemskova, M. A., Axenova, L. N., and Medvedev, A. E. 1997. Does isatin interact with rat brain monoamine oxidases in vitro? Neurosci. Lett. 233:58-60.
Burlet, A. J., Leon-Henri, B. P., Robert, F. R., Arachmani, A., Fernette, B. M., and Burlet, C. R. 1987. Monoclonal antivasopressin (VP) antibodies penetrate into VP neurons, in vivo. Exp. Brain Res. 65:629-638.
Kim, J. J., Shin, J. C., Chen, K., Chen, L., Bao, S., Maren, S., Anagnostards, S. G., Fanselow, M. S., De Maeyer, E., Seif, I., and Thompson, R. F. 1997. Selective enhancement of emotional, but not motor, learning in monoamine oxidase A deficient mice. Proc. Natl. Acad. Sci. USA 94:5929-5933.
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Danilova, R.A., Moskvityna, T.A., Obukhova, M.F. et al. Pargyline Conjugate-Induced Long-Term Activation of Monoamine Oxidase as an Immunological Model for Depression. Neurochem Res 24, 1147–1151 (1999). https://doi.org/10.1023/A:1020764504462
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DOI: https://doi.org/10.1023/A:1020764504462