The effects of typical and atypical antipsychotics on the electrical activity of the brain in a rat model

Abstract

Objective: Antipsychotic drugs are known to have strong effect on the bioelectric activity in the brain. However, some studies addressing the changes on electroencephalography (EEG) caused by typical and atypical antipsychotic drugs are conflicting. We aimed to compare the effects of typical and atypical antipsychotics on the electrical activity in the brain via EEG recordings in a rat model. Methods: Thirty-two Sprague Dawley adult male rats were used in the study. The rats were divided into five groups, randomly (n=7, for each group). The first group was used as control group and administered 1 ml/kg saline intraperitoneally (IP). Haloperidol (1 mg/kg) (group 2), chlorpromazine (5 mg/kg) (group 3), olanzapine (1 mg/kg) (group 4), ziprasidone (1 mg/ kg) (group 5) were injected IP for five consecutive days. Then, EEG recordings of each group were taken for 30 minutes. Results: The percentages of delta and theta waves in haloperidol, chlorpromazine, olanzapine and ziprasidone groups were found to have a highly significant difference compared with the saline administration group (p

Keywords

• Haloperidol, chlorpromazine, olanzapine, ziprasidone, EEG, rat

Rat modelinde tipik ve atipik antipsikotik ilaçların beyin elektriksel aktivitesi üzerine etkileri

Öz

Amaç: Antipsikotik ilaçların beyinde güçlü biyoelektrik aktivite etkilerinin olduğu bilinmektedir. Fakat tipik ve atipik antipsikotik ilaçlara bağlı olan elektroensefalografi (EEG) değişikliklerinin karşılaştırmalı çalışmaları tartışmalıdır. Biz bir rat modelinde tipik ve atipik antipsikotik ilaçların beyinde elektriksel aktivitesi üzerine olan etkilerini EEG ile karşılaştırmayı amaçladık. Yöntemler: Bu çalışmada, 35 adet erişkin erkek Sprague Dawley cinsi rat kullanıldı. Herbiri 7 adet rat içeren 5 adet grup oluşturuldu. Birinci grup kontrol grubu olarak kullanıldı ve intraperitoneal yolla 1 ml/kg salin verildi. Beş gün boyunca intraperitoneal olarak haloperidol (1 mg/kg) (grup 2), klorpromazin (5 mg/kg) (grup 3), olanzapin (1 mg/kg) (grup 4) ve ziprasidon (1 mg/kg) (grup 5) verildi. Beşinci günün sonunda bütün grupların 30 dakika EEG kaydı alındı. Bulgular: Haloperidol, klorpromazin, olanzapin ve ziprasidon gruplarında delta ve teta dalga yüzdelerinin salin verilen gruba göre anlamlı düzeyde yüksek olduğu görüldü (p

Anahtar Kelimeler

• Haloperidol, klorpromazin, olanzapin, ziprasidon, EEG, rat

Kaynakça

1. Dahl ML. Cytochrome p450 phenotyping/genotyping in patients receiving antipsychotics: useful aid to pre- scribing? Clin Pharmacokinet 2002;41:453-470.
2. Kaya C, Bulut M, Bez Y. Add-on treatment of aripip- razole in an adult onychophagia patient. J Clin Exp Invest 2012;3:545-547.
3. Zhou SF. Polymorphism of human cytochrome P450 2D6 and its clinical significance: part II. Clin Pharma- cokinet 2009;48:761-804.
4. Satterthwaite TD, Wolf DH, Rosenheck RA, Gur RE, Caroff SN. A meta-analysis of the risk of acute extra- pyramidal symptoms with intramuscular antipsychot- ics for the treatment of agitation. J Clin Psychiatry 2008;69:1869-1879.
5. Cavazzoni PA, Berg PH, Kryzhanovskaya LA, et al. Comparison of treatment-emergent extrapyramidal symptoms in patients with bipolar mania or schizo- phrenia during olanzapine clinical trials. J Clin Psy- chiatry 2006;67:107-113.
6. Cohrs S. Sleep disturbances in patients with schizo- phrenia: impact and effect of antipsychotics. CNS Drugs 2008;22:939-962.
7. Stip E. Cognition, schizophrenia and the effect of anti- psychotics. Encephale 2006;32:341-350.
8. Degner D, Nitsche MA, Bias F, et al. EEG alterations during treatment with olanzapine. Eur Arch Psychiatry Clin Neurosci 2011;261:483-488.

9. Arıkanoğlu A. Current approach to differential diagnosis of epileptic seizures and pseudo-seizures. J Clin Exp Invest 2011;2:330-334.
10. Small JG, Milstein V, Malloy FW, et al. Clinical and quantitative EEG studies of mania. J Affect Disord 1999;53:217-224.
11. Moore NC, Tucker KA, Brin FB, et al. Positive symp- toms of chizophrenia: response to haloperidol and remoxipride is associated with increased alpha EEG activity. Hum Psychopharmacol 1997;12:75-80.
12. Baldessarini RJ. Drugs and the treatment of psychi- atric disorders: depression and anxiety disorders, in Goodman and Gilman’s The Pharmacological Basis of Therapeutics, 10th ed. Edited by Hardman JG, Limbird LE, Gilman AG. New York, Mc.Graw-Hill, 2001;447-483.
13. Günther W, Baghai T, Naber D, et al. EEG alterations and seizures during treatment with clozapine. A retro- spective study of 283 patients. Pharmacopsychiatry 1993;26:69-74.
14. Pillmann F, Schlote K, Broich K, Marneros A. Elec- troencephalogram alterations during treatment with olanzapine. Psychopharmacology 2000;150:216-219.
15. Páleníček T, Fujáková M, Brunovský M, et al. Elec- troencephalographic spectral and coherence analy- sis of ketamine in rats: correlation with behavioral effects and pharmacokinetics. Neuropsychobiology 2011;63:202-218.
16. Bambal G, Çakıl D, Ekici F. Deneysel epilepsi model- leri. J Clin Exp Invest 2011;2:118-123.
17. Freedman R. Schizophrenia. N Engl J Med 2003;349:1738-1749.
18. Burns MJ. The pharmacology and toxicology of atypical antipsychotic agents. J Toxicol Clin Toxicol 2001;39:1-14.
19. Silvestri RC, Bromfield EB, Khoshbin S. Clozapine- induced seizures and EEG abnormalities in am- bulatory psychiatric patients. Ann Pharmacother 1998;32:1147-1151.
20. Devinsky O, Honigfeld G, Patin J. Clozapine-related seizures. Neurology 1991;41:369-371.
21. Aman BL, Pogarell O, Mergl R, et al. EEG abnormali- ties associated with antipsychotics: a comparison of quetiapine, olanzapine, haloperidol and healthy sub- jects. Hum Psychopharmacol 2003;18:641-646.
22. Wetzel H, Szegedi A, Hain C, et al. Seroquel (ICI-204- 636), a putative “atypical” antipsychotic, in schizo- phrenia with positive symptomatology: results of an open clinical trial and changes of neuroendocrinologi- cal and EEG parameters. Psychopharmacology (Berl) 1995;119:231-238.
23. Centorrino F, Price BH, Tuttle M, et al. EEG abnor- malities during treatment with typical and atypical an- tipsychotics. Am J Psychiatry 2002;159:109-115.
24. Hubl D, Kleinlogel H, Frolich L. Multilead quanti- tative electroencephalogram profile and cognitive evoked potentials (P300) in healthy subjects after a single dose of olanzapine. Psychopharmachology 2001;158:281-288.
25. Fink M. EEG and behavior: association or disassocia- tion in man? Integrative Psychiatry 1993;9:108-123.
26. Lee JW, Crismon ML, Dorson PG. Seizure associated with olanzapine. Ann Pharmacother 1999;33:554-556.
27. Fink M. EEG changes with antipsychotic drugs. Am J Psychiatry 2002;159:1439.