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The catalepsy in rats during chronic treatment with atypical neuroleptics; The different testing procedures
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Pharmacological Research, Vol . 25, Supplement 2, 1992
THE CATALEPSY IN RATS DURING CHRONIC TREATMENT WITH ATYPICAL NEUROLEPTICS ; THE DIFFERENT TESTING PROCEDURES Maria Bortel-Badura, Henryk I .Trzeciak Department of Pharmacology, Silesian School of Medicine, Medykow 18, 40-752 Katowice, Poland Key words : benzamides, catalepsy, rat
The pharmacological and toxicological effects after prolonged administration of classical neuroleptics are well known both in people and in animals . There have been few evidences about chronic treatment with atypical neuroleptics (benzamide derivatives) . A frequent test for the investigation of the behavioral effects of neuroleptics in rats is the catalepsy model . There are different data about cataleptogenic properties of atypical neuroleptics . Some authors described catalepsy in rats after administration of low doses of sulpiride [1] but others denied that phenomenon [2] . It is supposed that various testing procedures may be responsible for these differences . The aim of this study was to compare different scoring systems (minutes or points) used for estimation of the intensity of catalepsy in rats after chronic treatment with atypical neuroleptics (sulpiride, metoclopramide) and haloperidol . Material and methods Male Wistar rats weighing 170-190 g at the start of the experiments were used . The animals were treated intraperitoneally (i .p .) with haloperidol (2mg/kg) or sulpiride (50 and 100 mg/kg) or metoclopramide (20 and 40 mg/kg) daily for a period of 3 months . The rats were tested for catalepsy after a single drug administration and during chronic treatment (after one, two weeks and at monthly intervals respectively) . Catalepsy was measured according to the method of Simon et al . [3] and to the method described by Costall and Olley [4] . The intensity of catalepsy was estimated by using a numerical score [3,4] or in minutes [4] .Behavioral testing of catalepsy was carried out 1 .5, 3, 6, 9, 19 and 24 hours after the last drug administration . The area under the curve of twenty-four hours catalepsy was used to compare various testing procedures . The Mann-Whitney U-test was used for statistical evaluation . Results It was shown that both benzamide derivatives evoked catalepsy . The administration of sulpiride (single dose) induced a dosedependent catalepsy after a long latent period (3-4 h) with a maximal effect between 6-7 h . Metoclopramide in a single dose of 20 and 40 mg/kg i .p . produced catalepsy which developed after a short latent period (0 .5 h) with maximal effect between 4-5 h . The intesity of catalepsy induced by benzamide derivatives was significantly lower in comparison to haloperidol . It was stated that benzamide derivatives induced multiphasic catalepsy during
1043-6618/92/251100072/$03 .00/0
© 1992 The Italian Pharmacological Society
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Pharmacological Research, Vol . 25, Supplement 2, 1992
chronic treatment . Sulpiride in a dose of 50 and 100 mg/kg i .p . increased the catalepsy till the first month of experiment and subsequent decreased to the trace values after the second month . The increase of catalepsy was observed also in the third month of sulpiride administration . Metoclopramide in a dose of 20 mg/kg i .p . produced the similar multiphasic catalepsy effect during chronic treatment . It was shown significant differences between various methods of catalepsy estimation in rats . The highest intensity of catalepsy showed the rats examined in points by method of Simon et al . [3] . It was not stated statistical significant differences in catalepsy of rats estimated in points by method of Simon et al . [3] and method of Costall and Olley [4] . However the lowest intensity of catalepsy was observed in method described by Costall and Olley [4], when the minute scale was used . Conclusions 1 .The chronic treatment with benzamide derivatives induced multiphasic cataleptogenic effects in rats . 2 .The estimation in minute scale was the most objective method for measurements of catalepsy in rats . References 1 .Elliot PNC, Jenner P, Huizing G, Marsden CD, Miller R . Substituted benzamides as cerebral dopamine antagonists in rodents . Neuropharmacology 1977, 16 :333-42 . 2 .Worms P . Behavioral pharmacology of the benzamides as compared to standard neuroleptics . In : Stanley M, Rotrosen J, eds . The benzamides . New York : Raven Press, 1982 :7-16 . 3 .Simon P, Langwinski R, Boissier JR . Comparison de differents test d'evaluation de la catalepsie chez le rat . Therapie 1969, 24 :985-95 . 4 .Costall B, Olley JE . Cholinergic-and neuroleptic-induced catalepsy : modification by lesions in the caudate-putamen . Neuropharmacology 1971, 10 :297-306 .
Pharmacological Research, Vol . 25, Supplement 2, 1992
THE CATALEPSY IN RATS DURING CHRONIC TREATMENT WITH ATYPICAL NEUROLEPTICS ; THE DIFFERENT TESTING PROCEDURES Maria Bortel-Badura, Henryk I .Trzeciak Department of Pharmacology, Silesian School of Medicine, Medykow 18, 40-752 Katowice, Poland Key words : benzamides, catalepsy, rat
The pharmacological and toxicological effects after prolonged administration of classical neuroleptics are well known both in people and in animals . There have been few evidences about chronic treatment with atypical neuroleptics (benzamide derivatives) . A frequent test for the investigation of the behavioral effects of neuroleptics in rats is the catalepsy model . There are different data about cataleptogenic properties of atypical neuroleptics . Some authors described catalepsy in rats after administration of low doses of sulpiride [1] but others denied that phenomenon [2] . It is supposed that various testing procedures may be responsible for these differences . The aim of this study was to compare different scoring systems (minutes or points) used for estimation of the intensity of catalepsy in rats after chronic treatment with atypical neuroleptics (sulpiride, metoclopramide) and haloperidol . Material and methods Male Wistar rats weighing 170-190 g at the start of the experiments were used . The animals were treated intraperitoneally (i .p .) with haloperidol (2mg/kg) or sulpiride (50 and 100 mg/kg) or metoclopramide (20 and 40 mg/kg) daily for a period of 3 months . The rats were tested for catalepsy after a single drug administration and during chronic treatment (after one, two weeks and at monthly intervals respectively) . Catalepsy was measured according to the method of Simon et al . [3] and to the method described by Costall and Olley [4] . The intensity of catalepsy was estimated by using a numerical score [3,4] or in minutes [4] .Behavioral testing of catalepsy was carried out 1 .5, 3, 6, 9, 19 and 24 hours after the last drug administration . The area under the curve of twenty-four hours catalepsy was used to compare various testing procedures . The Mann-Whitney U-test was used for statistical evaluation . Results It was shown that both benzamide derivatives evoked catalepsy . The administration of sulpiride (single dose) induced a dosedependent catalepsy after a long latent period (3-4 h) with a maximal effect between 6-7 h . Metoclopramide in a single dose of 20 and 40 mg/kg i .p . produced catalepsy which developed after a short latent period (0 .5 h) with maximal effect between 4-5 h . The intesity of catalepsy induced by benzamide derivatives was significantly lower in comparison to haloperidol . It was stated that benzamide derivatives induced multiphasic catalepsy during
1043-6618/92/251100072/$03 .00/0
© 1992 The Italian Pharmacological Society
8
Pharmacological Research, Vol . 25, Supplement 2, 1992
chronic treatment . Sulpiride in a dose of 50 and 100 mg/kg i .p . increased the catalepsy till the first month of experiment and subsequent decreased to the trace values after the second month . The increase of catalepsy was observed also in the third month of sulpiride administration . Metoclopramide in a dose of 20 mg/kg i .p . produced the similar multiphasic catalepsy effect during chronic treatment . It was shown significant differences between various methods of catalepsy estimation in rats . The highest intensity of catalepsy showed the rats examined in points by method of Simon et al . [3] . It was not stated statistical significant differences in catalepsy of rats estimated in points by method of Simon et al . [3] and method of Costall and Olley [4] . However the lowest intensity of catalepsy was observed in method described by Costall and Olley [4], when the minute scale was used . Conclusions 1 .The chronic treatment with benzamide derivatives induced multiphasic cataleptogenic effects in rats . 2 .The estimation in minute scale was the most objective method for measurements of catalepsy in rats . References 1 .Elliot PNC, Jenner P, Huizing G, Marsden CD, Miller R . Substituted benzamides as cerebral dopamine antagonists in rodents . Neuropharmacology 1977, 16 :333-42 . 2 .Worms P . Behavioral pharmacology of the benzamides as compared to standard neuroleptics . In : Stanley M, Rotrosen J, eds . The benzamides . New York : Raven Press, 1982 :7-16 . 3 .Simon P, Langwinski R, Boissier JR . Comparison de differents test d'evaluation de la catalepsie chez le rat . Therapie 1969, 24 :985-95 . 4 .Costall B, Olley JE . Cholinergic-and neuroleptic-induced catalepsy : modification by lesions in the caudate-putamen . Neuropharmacology 1971, 10 :297-306 .