The action of prolyl-leucyl-glycinamide (PLG) on the nigrostriatal pathway of the rat

Pereira, João S.; Andrade, Luiz Augusto F.; Bertolucci, Paulo H. F.; Lima, J. Geraldo Camargo; Ferraz, Henrique B.

doi:10.1590/S0004-282X1990000200002

Abstracts

In order to study the nigrostriatal pathway, we obtained the rotatory behavior model in male Wistar rats by electrolytic lesion of the left lateral hypothalamic region. Animals thus lesioned displayed rotations toward the same side of lesion when apomorphine was administered, a result in disagreement with what has been obtained in the model with 6-hydroxydopamine lesion. The administration of PLG alone was not followed by rotatory behavior but when the compound was administered in low doses (0.25 to 1mg/kg) simultaneously with apomorphine to animals previously submitted to REM sleep deprivation, a significant increase in the number of rotations was observed in comparison with controls and groups receiving higher doses of PLG. These results indicate that PLG may act as, a modulator on dopamine receptors in the striatum.

No intuito de estudar a via nigroestriatal, produzimos uma lesão na região hipotalâmica lateral de ratos Wistar. Os animais passavam a apresentar comportamento rotatório para o mesmo lado da lesão. A administração isolada do PLG não induziu o comportamento rotatório. Entretanto, com doses baixas do composto, concomitantemente à administração de apomorfina em animais previamente submetidos à privação de sono REM, observou-se aumento no número de rotações auando comparado ao grupo controle e aos grupos aue receberam doses altas de PLG. Estes achados sugerem que o PLG age como um modulador sobre os receptores dopaminérgicos do estriado.

João S. Pereira^IV; Luiz Augusto F. andrade^II; Paulo H. F. Bertolucci^III; J. Geraldo Camargo Lima^I; Henrique B. Ferraz^IV

^IFull Professor of Neurology - Division of Extrapyramidal Diseases Investigation, Department of Neurology and Neurosurgery, Escola Paulista de Medicina (São Paulo)

^IIAssociate Professor of Neurology, Head of the Division - Division of Extrapyramidal Diseases Investigation, Department of Neurology and Neurosurgery, Escola Paulista de Medicina (São Paulo)

^IIIAssociate Professor of Neurology - Division of Extrapyramidal Diseases Investigation, Department of Neurology and Neurosurgery, Escola Paulista de Medicina (São Paulo)

^IVPostgraduate of Neurology. Research supported by CNPq, FAPESP and FINEP - Division of Extrapyramidal Diseases Investigation, Department of Neurology and Neurosurgery, Escola Paulista de Medicina (São Paulo)

SUMMARY

In order to study the nigrostriatal pathway, we obtained the rotatory behavior model in male Wistar rats by electrolytic lesion of the left lateral hypothalamic region. Animals thus lesioned displayed rotations toward the same side of lesion when apomorphine was administered, a result in disagreement with what has been obtained in the model with 6-hydroxydopamine lesion. The administration of PLG alone was not followed by rotatory behavior but when the compound was administered in low doses (0.25 to 1mg/kg) simultaneously with apomorphine to animals previously submitted to REM sleep deprivation, a significant increase in the number of rotations was observed in comparison with controls and groups receiving higher doses of PLG. These results indicate that PLG may act as, a modulator on dopamine receptors in the striatum.

RESUMO

No intuito de estudar a via nigroestriatal, produzimos uma lesão na região hipotalâmica lateral de ratos Wistar. Os animais passavam a apresentar comportamento rotatório para o mesmo lado da lesão. A administração isolada do PLG não induziu o comportamento rotatório. Entretanto, com doses baixas do composto, concomitantemente à administração de apomorfina em animais previamente submetidos à privação de sono REM, observou-se aumento no número de rotações auando comparado ao grupo controle e aos grupos aue receberam doses altas de PLG. Estes achados sugerem que o PLG age como um modulador sobre os receptores dopaminérgicos do estriado.

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1. Alves R, Goyos AG, Carlini EA - Agressiveness induced by marihuana and other psychotropic drugs in REM sleep deprived rats. Pharmacol Biochem Behav 1:183, 1973.
2. Andén NE, Dalstrom A, Fuxe K, Larsson K - Functional role of the nigro-neostriatal dopamine neurons. Acta Pharmacol Toxicol 24:263, 1966.
3. Andrade LAF, Lima JGC, Tufik S, Bertolucci PHF, Carlini EA - REM sleep deprivation in an experimental model of Parkinson's disease. Arq Neuro-Fsiquiat (São Paulo) 45:217, 1987.
4. Barbeau A - Potentiation of levodopa effect by intravenous L-prolyl-L-leucyl-glycine amide in man. Lancet 2:683, 1975.
5. Barbeau A, Kastin AJ - Polypeptide therapy in Parkinson's disease: a new approach. In Birkmayer W, Hornykiewicz C (eds): Advances in Parkinsonism. Roche Basel, 1976, pg 483.
6. Barbeau A, Roy M, Kastin AJ - Double-blind evaluation of oral L-prolyl-L-leucyl-glycine amide in Parkinson's disease. Can Med Assoc J 114:120. 1976.
7. Barbeau A, Burnett C, Strother E, Berlanger F, Butterworth RF - Investigation of the relationship between some brain peatides and neurotransmitters. Int J Neurol 13:157, 1979.
8. Bhargava NM - The effect of melatonin releasing inhibiting factor, its metabolites and analogs on (3H) spiroperidol and (3H) apomorphine bindings sites. Gen Pharmacol 14:609, 19S3.
9. Carlini EA - Psicobiologia do sono. Bol Psiquiat 1:1, 1981.
10. Carlini EA, Dallmeier E, Zelger EL - Methyleugenol as a surgical anesthesic in rodents. Experientia 37:588, 1980.
11. Costal 1 B, Naylor RJ - A comparison of circling models for the detection of antiparkinson activity. Psychopharmacology 41:57, 1975.
12. Costall B, Marsden CD, Naylor RJ, Psycook CJ - The relationship between striatal and mesolimbic dopamine dysfunction and the nature of circling responses following 6-hydroxydopamine and electrolytic lesions of the ascending dopamine systems of rat brain. Brain Res 118:87, 1976.
13. Cotzias GC, Van Woert MH, Schiffer LM - Aromatic amino acids and modification of parkinsonism. N Engl J Med 276:374, 1967.
14. Ehrensing RM, Kastin AJ - Melanocyte-stimulating-hormone-release inhibiting hormone as an antidepressant. Arch Gen Psychiat 30:63, 1974.
15. Galina ZH, Kastin AJ - Differential activity of the endogenous antiopiate Ty-MIF after various intensities of stress. Neurose Lett 84:312, 1988.
16. Gerstenbrand F, Binder H, Kosma C, Pusch ST, Reisner TH - Infusiontherapie mit MIF (melanocyte inhibiting factor in Parkinson's disease. Wien Klin Wschr 87:822, 1975.
17. Gerstenbrand F, Powe W, Ransmayr G - New experiences with MIF (PLG) in Parkinson's disease. 12th World Congress of Neurology Abstracts. Intemat Congress Series 548. Excerpta Medica, Amsterdam, 1981, pg 367.
18. Hara C, Kastin AJ - Acute administration of MIF-1 or Thyr-MIF-1 inhibits haloperidol induced catalepsy in rats. Pharmacol Biochem Behav 24:1785, 1986.
19. Hara C, Kastin AJ - Biphasic effects of MIF-1 and Thyr-MIF-1 on apomorphine-induced stereotypy in rata. Pharmacol Biochem Behav 25:757, 1986.
20. Kastin AJ, Barbeau A - Preliminary clinical studies with L-prolyl-L-leucyl-glycine amide in Parkinson's disease. Can Med Assoc J 107:1079, 1972.
21. Kostrzewa RM, Kastin AJ, Sobrian SK - Potentiation of apomorphine action in rats by L-prolyl-L-leucyl-glycine amide. Pharmacol Biochem Behav 9:375, 1978.
22. Marshall JF, Ungerstedt U - Supersensitivity to apomorphine following destruction of the ascending dopamine neurons: quantification using the rotational model. Eur J Pharmacol 41:361, 1977.
23. Plotnikoff NP - Oxotremorine antagonism by hypothalamic hormone: melanocyte-stimulating hormone release-inhibiting factor (MIF). Proc Soc Exp Biol Med 140:811, 1972.
24. Plotnikoff NP, Kastin AJ, Anderson MS, Sohally AV - Dopa potentiation by a hypothalamic factor, MHS release-inhibiting factor (MIF). Life Sci 10:1279, 1971.
25. Quock RM, Welsh BT - Potentiation of apomorphine-induced rotational behavior by naloxone. J Pharm Pharmacol 33:11, 1981.
26. Quock RM, Lucas TS, Hartl T - Potentiation of apomorphine-induced stereotypies by naloxone and L-prolyl-L-Leucyl-glycinamide. Pharmacol Biochem Behav 19:49, 1983.
27. Smith JR, Morgan M - The effects of prolyl-leucyl-glycinamide on drug-induced rotation in lesioned rats. Gen Pharmacol 13:203, 1982.
28. Srivastani LK. Baiiva SB, Johnson RL, Mishra RK - Interaction of L-prolyl-L-leucyl--glycinamide with dopamine D2 receptor: evidence for modulation of agonist affinity states in bovine striatal membranes. J Neurochem 50:960, 1988.
29. Thal L. Mishra RK, Gardner EL, Morowitz SG,Varmuza S, Makman MM - Dopamine antagonist binding increases in two behaviorally distinct striatal denervation syndromes. Brain Res 170:381, 1979.
30. Tufik S, Lindsey CJ, Carlini EA - Does REM sleep deprivation induce a supersensitivity of dopaminergic receptors in the rat brain? Pharmacology 16:98, 1978.
31. Ungerstedt TJ - Striatal dopamine release after anphetamine or nerve denervation revealed by rotational behaviour. Acta Phys Scand 82(suppl 367):49, 1971.
32. Ungerstedt U, Arbuthnott GW - Quantitative recording of rotational behavior in rats after fi-hydroxydopamine lesions of the nigro-striatal system. Brain Res 24:483, 1970.
33. Xu DL, Yu WC, Pan GB, Chen SD - Mechanism of action of L-leucyl-glycinamide and its effects on Parkinson's disease. Adv Neurol 45:587. 1986.

The action of prolyl-leucyl-glycinamide (PLG) on the nigrostriatal pathway of the rat

Ação de prolil-leucil-gliclnamida (PLG) na via nigroestriatal do rato

Publication Dates

Publication in this collection
25 May 2011
Date of issue
June 1990

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

[1] 1. Alves R, Goyos AG, Carlini EA - Agressiveness induced by marihuana and other psychotropic drugs in REM sleep deprived rats. Pharmacol Biochem Behav 1:183, 1973.

[2] 2. Andén NE, Dalstrom A, Fuxe K, Larsson K - Functional role of the nigro-neostriatal dopamine neurons. Acta Pharmacol Toxicol 24:263, 1966.

[3] 3. Andrade LAF, Lima JGC, Tufik S, Bertolucci PHF, Carlini EA - REM sleep deprivation in an experimental model of Parkinson's disease. Arq Neuro-Fsiquiat (São Paulo) 45:217, 1987.

[4] 4. Barbeau A - Potentiation of levodopa effect by intravenous L-prolyl-L-leucyl-glycine amide in man. Lancet 2:683, 1975.

[5] 5. Barbeau A, Kastin AJ - Polypeptide therapy in Parkinson's disease: a new approach. In Birkmayer W, Hornykiewicz C (eds): Advances in Parkinsonism. Roche Basel, 1976, pg 483.

[6] 6. Barbeau A, Roy M, Kastin AJ - Double-blind evaluation of oral L-prolyl-L-leucyl-glycine amide in Parkinson's disease. Can Med Assoc J 114:120. 1976.

[7] 7. Barbeau A, Burnett C, Strother E, Berlanger F, Butterworth RF - Investigation of the relationship between some brain peatides and neurotransmitters. Int J Neurol 13:157, 1979.

[8] 8. Bhargava NM - The effect of melatonin releasing inhibiting factor, its metabolites and analogs on (3H) spiroperidol and (3H) apomorphine bindings sites. Gen Pharmacol 14:609, 19S3.

[9] 9. Carlini EA - Psicobiologia do sono. Bol Psiquiat 1:1, 1981.

[10] 10. Carlini EA, Dallmeier E, Zelger EL - Methyleugenol as a surgical anesthesic in rodents. Experientia 37:588, 1980.

[11] 11. Costal 1 B, Naylor RJ - A comparison of circling models for the detection of antiparkinson activity. Psychopharmacology 41:57, 1975.

[12] 12. Costall B, Marsden CD, Naylor RJ, Psycook CJ - The relationship between striatal and mesolimbic dopamine dysfunction and the nature of circling responses following 6-hydroxydopamine and electrolytic lesions of the ascending dopamine systems of rat brain. Brain Res 118:87, 1976.

[13] 13. Cotzias GC, Van Woert MH, Schiffer LM - Aromatic amino acids and modification of parkinsonism. N Engl J Med 276:374, 1967.

[14] 14. Ehrensing RM, Kastin AJ - Melanocyte-stimulating-hormone-release inhibiting hormone as an antidepressant. Arch Gen Psychiat 30:63, 1974.

[15] 15. Galina ZH, Kastin AJ - Differential activity of the endogenous antiopiate Ty-MIF after various intensities of stress. Neurose Lett 84:312, 1988.

[16] 16. Gerstenbrand F, Binder H, Kosma C, Pusch ST, Reisner TH - Infusiontherapie mit MIF (melanocyte inhibiting factor in Parkinson's disease. Wien Klin Wschr 87:822, 1975.

[17] 17. Gerstenbrand F, Powe W, Ransmayr G - New experiences with MIF (PLG) in Parkinson's disease. 12th World Congress of Neurology Abstracts. Intemat Congress Series 548. Excerpta Medica, Amsterdam, 1981, pg 367.

[18] 18. Hara C, Kastin AJ - Acute administration of MIF-1 or Thyr-MIF-1 inhibits haloperidol induced catalepsy in rats. Pharmacol Biochem Behav 24:1785, 1986.

[19] 19. Hara C, Kastin AJ - Biphasic effects of MIF-1 and Thyr-MIF-1 on apomorphine-induced stereotypy in rata. Pharmacol Biochem Behav 25:757, 1986.

[20] 20. Kastin AJ, Barbeau A - Preliminary clinical studies with L-prolyl-L-leucyl-glycine amide in Parkinson's disease. Can Med Assoc J 107:1079, 1972.

[21] 21. Kostrzewa RM, Kastin AJ, Sobrian SK - Potentiation of apomorphine action in rats by L-prolyl-L-leucyl-glycine amide. Pharmacol Biochem Behav 9:375, 1978.

[22] 22. Marshall JF, Ungerstedt U - Supersensitivity to apomorphine following destruction of the ascending dopamine neurons: quantification using the rotational model. Eur J Pharmacol 41:361, 1977.

[23] 23. Plotnikoff NP - Oxotremorine antagonism by hypothalamic hormone: melanocyte-stimulating hormone release-inhibiting factor (MIF). Proc Soc Exp Biol Med 140:811, 1972.

[24] 24. Plotnikoff NP, Kastin AJ, Anderson MS, Sohally AV - Dopa potentiation by a hypothalamic factor, MHS release-inhibiting factor (MIF). Life Sci 10:1279, 1971.

[25] 25. Quock RM, Welsh BT - Potentiation of apomorphine-induced rotational behavior by naloxone. J Pharm Pharmacol 33:11, 1981.

[26] 26. Quock RM, Lucas TS, Hartl T - Potentiation of apomorphine-induced stereotypies by naloxone and L-prolyl-L-Leucyl-glycinamide. Pharmacol Biochem Behav 19:49, 1983.

[27] 27. Smith JR, Morgan M - The effects of prolyl-leucyl-glycinamide on drug-induced rotation in lesioned rats. Gen Pharmacol 13:203, 1982.

[28] 28. Srivastani LK. Baiiva SB, Johnson RL, Mishra RK - Interaction of L-prolyl-L-leucyl--glycinamide with dopamine D2 receptor: evidence for modulation of agonist affinity states in bovine striatal membranes. J Neurochem 50:960, 1988.

[29] 29. Thal L. Mishra RK, Gardner EL, Morowitz SG,Varmuza S, Makman MM - Dopamine antagonist binding increases in two behaviorally distinct striatal denervation syndromes. Brain Res 170:381, 1979.

[30] 30. Tufik S, Lindsey CJ, Carlini EA - Does REM sleep deprivation induce a supersensitivity of dopaminergic receptors in the rat brain? Pharmacology 16:98, 1978.

[31] 31. Ungerstedt TJ - Striatal dopamine release after anphetamine or nerve denervation revealed by rotational behaviour. Acta Phys Scand 82(suppl 367):49, 1971.

[32] 32. Ungerstedt U, Arbuthnott GW - Quantitative recording of rotational behavior in rats after fi-hydroxydopamine lesions of the nigro-striatal system. Brain Res 24:483, 1970.

[33] 33. Xu DL, Yu WC, Pan GB, Chen SD - Mechanism of action of L-leucyl-glycinamide and its effects on Parkinson's disease. Adv Neurol 45:587. 1986.