Privação de sono REM em um modelo experimental da doença de Parkinson

Andrade, Luiz A. F.; Lima, José G. C.; Tufik, Sérgio; Bertolucci, Paulo H. F.; Carlini, E. A.

doi:10.1590/S0004-282X1987000300001

Resumos

Investigação prévia mostrou que ratos privados de sono (REM SD) mostram acentuação de resposta a agonistas dopaminérgicos. As evidências indicam que essa ação parece ser mediada por supersensibilização de receptores dopaminérgicos pós-sinápticos. Com base nisso, foi feita REM SD em ratos com modelo experimental da doença de Parkinson, nos quais foi feita lesão eletrolítica bilateral de ambas as vias nigro-estriatais. Sete dias após a cirurgia os animais eram submetidos a REM SD por 72 horas. Imediatamente após o final deste período era feita observação em campo aberto para a ambulação, "rearing", "grooming" e latência. Em comparação com ratos não-privados foi observado aumento significativo na ambulação e "rearing", resposta que reapareceu após um segundo período de REM SD, realizado 21 dias após a cirurgia. Estes dados, de melhora de dois parâmetros de modelo experimental da doença de Parkinson, sugerem que a privação de sono pode ser útil nesta doença.

Previous investigations have shown that REM sleep deprived (REM SD) rats display an enhanced response to dopamine agonists. This action seems to be mediated through a supersensitivity of dopamine post-synaptic receptors. Accordingly, REM SD was performed on rats with an experimental model of Parkinson's disease. The animals were bilaterally lesioned in the nigrostriatal pathway through a stereotaxically directed electrical current. Seven days after the surgery the animals were REM SD for 72 hours and immediatelly after the end of this period were observed in an open field for ambulation, rearing, grooming, and latency. In comparison with non-deprived rats there was a significant increase in ambulation and rearing, a response that appeared again after a second REM SD period on day 21th after the surgery. These data of improvement of two parameters of an experimental model of Parkinson's disease suggest that SD may be useful in this condition.

REM sleep deprivation in an experimental model of Parkinson's disease

Privação de sono REM em um modelo experimental da doença de Parkinson

Luiz A. F. Andrade^I; José G. C. Lima^I; Sérgio Tufik^II; Paulo H. F. Bertolucci^I; E. A. Carlini^II

^IDepartments of Neurology and Neurosurgery - Escola Paulista de Medicina, São Paulo, Brazil. Work partially supported by CNPq and FINEP. P.H.F.B. was a fellow from FAPESP (Proc. 83/1307-5). This work received the Henrique Sam Mindlin Award of the Brazilian Academy of Neurology (1982)

^IIPsychobiology - Escola Paulista de Medicina, São Paulo, Brazil. Work partially supported by CNPq and FINEP. P.H.F.B. was a fellow from FAPESP (Proc. 83/1307-5) This work received the Henrique Sam Mindlin Award of the Brazilian Academy of Neurology (1982)

SUMMARY

Previous investigations have shown that REM sleep deprived (REM SD) rats display an enhanced response to dopamine agonists. This action seems to be mediated through a supersensitivity of dopamine post-synaptic receptors. Accordingly, REM SD was performed on rats with an experimental model of Parkinson's disease. The animals were bilaterally lesioned in the nigrostriatal pathway through a stereotaxically directed electrical current. Seven days after the surgery the animals were REM SD for 72 hours and immediatelly after the end of this period were observed in an open field for ambulation, rearing, grooming, and latency. In comparison with non-deprived rats there was a significant increase in ambulation and rearing, a response that appeared again after a second REM SD period on day 21th after the surgery. These data of improvement of two parameters of an experimental model of Parkinson's disease suggest that SD may be useful in this condition.

RESUMO

Investigação prévia mostrou que ratos privados de sono (REM SD) mostram acentuação de resposta a agonistas dopaminérgicos. As evidências indicam que essa ação parece ser mediada por supersensibilização de receptores dopaminérgicos pós-sinápticos. Com base nisso, foi feita REM SD em ratos com modelo experimental da doença de Parkinson, nos quais foi feita lesão eletrolítica bilateral de ambas as vias nigro-estriatais. Sete dias após a cirurgia os animais eram submetidos a REM SD por 72 horas. Imediatamente após o final deste período era feita observação em campo aberto para a ambulação, "rearing", "grooming" e latência. Em comparação com ratos não-privados foi observado aumento significativo na ambulação e "rearing", resposta que reapareceu após um segundo período de REM SD, realizado 21 dias após a cirurgia. Estes dados, de melhora de dois parâmetros de modelo experimental da doença de Parkinson, sugerem que a privação de sono pode ser útil nesta doença.

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Departamento de Neurologia e Neurocirurgia - Escola Paulista de Medicina - Rua Botucatu, 740 - 04023 - São Paulo, SP - Brasil.

Referências bibliográficas

1. ALVES, C.N.; GOYOS, A.C. & CARLINI, E.A. - Aggressiveness induced by marihuana and other psychotropic drugs in REM sleep deprived rats.. Pharmacol. Biochem. Behav. 1:183, 1983.
2. AMIN, M. - Response to sleep deprivation and therapeutic results with antidepressants. Lancet 2:165, 1978.
3. CARLINI, B.A. & LINDSEY, C.J. - Pharmacological manipulations of brain catecholamines and the aggressive behavior induced by marihuana in REM-sleep deprived rats. Aggressive Behav. 1:81, 1974.
4. CHRISTODOULOU, G.N.; MALLIARAS, D.E.; LYKOURAS, E.P.; PAPADIMITIOU. G.N. & STEFANIS, C.N. - Possible prophylatic effect of sleep deprivation. Amer. J. Psychiat. 135:375, 1978.
5. CREESE, I.; BURT, D.R. & SNYDER, S.H. - Dopamine receptor binding: differentiation of agonist and antagonist states with 3 H-dopamine and 3 G-haloperidol. Life Sci. 17:993, 1976.
6. FERGUSON, J. & DEMENT, W. - The behavioral effects of amphetamine on REM deprived rats. J. psychiat. Res. 7:111, 1969.
7. HALARIS, A.E. & FREEDMAN, D.X. - Psychotropic drugs and dopamine uptake inhibition. Res. Publ. Assoc. nerv. ment. Dis. 54:248, 1975.
8. HUNT, P.; KANNENGIESSER, M.H. & RAYNAUD, J.P. - Nomifensine: a new potent inhibitor of dopamine uptake into synaptosomes from rat brain corpus striatum. J. Pharm. Pharmacol. 26:370, 1974.
9. LARSEN, J.K.; LINDBERG, M.L. & SKOVGAARD, B. - Sleep deprivation as treatment for endogenous depression. Acta psychiat. Scand. 54:167, 1976.
10. LEE, T.; SEEM AN, P.; RAJPUT, A.; FARLEY, I.J. & HORNYKIEWICZ, O. - Receptor basis for dopaminergic supersensitivity in Parkinson's disease. Nature 273:59, 1978.
11. MARSHALL, J.F.; LEVITAN, D. & STRICKER, E.M. - Activation-induced restoration of sensorimotor functions in rats with dopamine-depleting brain lesions. J. comp. Physiol. Psychol. 90:536, 1976.
12. PFLUG, B. & TÖLLE, R. - Disturbance of the 24-hours rhythm in endogenous depression by sleep deprivation. Int. Pharmacopsychiat. 6:187, 1971.
13. RANDRUP, A. & BRAESTRUP, C. - Uptake inhibition of biogenic amines by newer antidepressant drugs: relevance to the dopamine hypothesis of depression. Psychopharmacology 53:309, 1977.
14. RIDDAL, D.R & LEAVENS, W.J. - Affinities of drugs for the agonist and antagonist states of the dopamine receptor. Eur. J. Pharmacol. 51:187, 1978.
15. TUFIK, S. - Increased responsiveness to apomorphine after REM sleep deprivation: supersensitivity of dopamine receptors or increase in dopamine turnover? J. Pharm. Pharmacol. 33:732, 1981.
16. Van den BURG, W. & van den HOOFDAKKER, R.H. - Total sleep deprivation in endogenous depression. Arch, gen, Psychiat. 32:1121, 1975.

Datas de Publicação

Publicação nesta coleção
22 Jun 2011
Data do Fascículo
Set 1987

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

[1] 1. ALVES, C.N.; GOYOS, A.C. & CARLINI, E.A. - Aggressiveness induced by marihuana and other psychotropic drugs in REM sleep deprived rats.. Pharmacol. Biochem. Behav. 1:183, 1983.

[2] 2. AMIN, M. - Response to sleep deprivation and therapeutic results with antidepressants. Lancet 2:165, 1978.

[3] 3. CARLINI, B.A. & LINDSEY, C.J. - Pharmacological manipulations of brain catecholamines and the aggressive behavior induced by marihuana in REM-sleep deprived rats. Aggressive Behav. 1:81, 1974.

[4] 4. CHRISTODOULOU, G.N.; MALLIARAS, D.E.; LYKOURAS, E.P.; PAPADIMITIOU. G.N. & STEFANIS, C.N. - Possible prophylatic effect of sleep deprivation. Amer. J. Psychiat. 135:375, 1978.

[5] 5. CREESE, I.; BURT, D.R. & SNYDER, S.H. - Dopamine receptor binding: differentiation of agonist and antagonist states with 3 H-dopamine and 3 G-haloperidol. Life Sci. 17:993, 1976.

[6] 6. FERGUSON, J. & DEMENT, W. - The behavioral effects of amphetamine on REM deprived rats. J. psychiat. Res. 7:111, 1969.

[7] 7. HALARIS, A.E. & FREEDMAN, D.X. - Psychotropic drugs and dopamine uptake inhibition. Res. Publ. Assoc. nerv. ment. Dis. 54:248, 1975.

[8] 8. HUNT, P.; KANNENGIESSER, M.H. & RAYNAUD, J.P. - Nomifensine: a new potent inhibitor of dopamine uptake into synaptosomes from rat brain corpus striatum. J. Pharm. Pharmacol. 26:370, 1974.

[9] 9. LARSEN, J.K.; LINDBERG, M.L. & SKOVGAARD, B. - Sleep deprivation as treatment for endogenous depression. Acta psychiat. Scand. 54:167, 1976.

[10] 10. LEE, T.; SEEM AN, P.; RAJPUT, A.; FARLEY, I.J. & HORNYKIEWICZ, O. - Receptor basis for dopaminergic supersensitivity in Parkinson's disease. Nature 273:59, 1978.

[11] 11. MARSHALL, J.F.; LEVITAN, D. & STRICKER, E.M. - Activation-induced restoration of sensorimotor functions in rats with dopamine-depleting brain lesions. J. comp. Physiol. Psychol. 90:536, 1976.

[12] 12. PFLUG, B. & TÖLLE, R. - Disturbance of the 24-hours rhythm in endogenous depression by sleep deprivation. Int. Pharmacopsychiat. 6:187, 1971.

[13] 13. RANDRUP, A. & BRAESTRUP, C. - Uptake inhibition of biogenic amines by newer antidepressant drugs: relevance to the dopamine hypothesis of depression. Psychopharmacology 53:309, 1977.

[14] 14. RIDDAL, D.R & LEAVENS, W.J. - Affinities of drugs for the agonist and antagonist states of the dopamine receptor. Eur. J. Pharmacol. 51:187, 1978.

[15] 15. TUFIK, S. - Increased responsiveness to apomorphine after REM sleep deprivation: supersensitivity of dopamine receptors or increase in dopamine turnover? J. Pharm. Pharmacol. 33:732, 1981.

[16] 16. Van den BURG, W. & van den HOOFDAKKER, R.H. - Total sleep deprivation in endogenous depression. Arch, gen, Psychiat. 32:1121, 1975.