Table of Contents  
RESEARCH LETTER
Year : 2013  |  Volume : 4  |  Issue : 4  |  Page : 283-285  

Modulation of conditioned avoidance response and quetiapine-induced metabolic syndrome by rosuvastatin and CDP-choline in rats


Department of Pharmacolgy, Faculty of Pharmacy, Jamia Hamdard, New Delhi, India

Date of Web Publication10-Oct-2013

Correspondence Address:
Ahmad Shafique
Department of Pharmacology, Faculty of Pharmacy, Hamdard University, New Delhi
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0976-500X.119715

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How to cite this article:
Shafique A, Pillai K K, Hasan AA, Najmi A K. Modulation of conditioned avoidance response and quetiapine-induced metabolic syndrome by rosuvastatin and CDP-choline in rats. J Pharmacol Pharmacother 2013;4:283-5

How to cite this URL:
Shafique A, Pillai K K, Hasan AA, Najmi A K. Modulation of conditioned avoidance response and quetiapine-induced metabolic syndrome by rosuvastatin and CDP-choline in rats. J Pharmacol Pharmacother [serial online] 2013 [cited 2019 Jul 21];4:283-5. Available from: http://www.jpharmacol.com/text.asp?2013/4/4/283/119715

Sir,

Metabolic syndrome diabetes mellitus, lipid abnormalities, and weight gain have increasingly been recognized with the use of the newer, atypical antipsychotic drugs like quetiapine. The prevalence of metabolic syndrome in these studies was around 40%. [1],[2] Physical disorders such as obesity, hyperlipidemia, hypertension, and type-2 diabetes mellitus are becoming recognized as significant comorbidities in patients with bipolar disorder (BD). [3] Atypical antipsychotics are one of the important treatment options for bipolar patients who are manic and/or psychotic. However, in recent years, there has been growing concern about the potential metabolic side effects of antipsychotics. [4],[5] In this regards study was conducted to find out the effect on glucose, serum triglyceride, and liver glycogen with combination of quetiapine (QT) with rosuvastatin (RS) and QT with cytidine diphosphate-choline (CDC) in CAR-induced rats.

The rats (Wistar rat) were divided into nine groups, each group containing eight rats. In this study, psychotic symptoms were induced in rats through Conditioned Avoidance Response (CAR) using Cook's pole climbing apparatus. After the induction of CAR training of animal for 7 days, drug treatment was given for 21 days [Table 1]. On 22 nd day under light anesthesia 1 ml of blood was collected through retro-orbital sinus [6] for estimation of blood glucose and triglyceride level and then the animals were sacrificed to determine the liver glycogen concentration. This study was approved by the Institutional Animal Ethics Committee, Jamia Hamdard, New Delhi. Statistical analysis used mean ± SEM, analysis of variance (ANOVA), followed by Dunnett's t-test. Values were considered statistically significant, when P < 0.05.
Table 1: Treatment schedule

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Effect of quetiapine, rosuvastatin, and CDP-choline alone and in combination on blood glucose, triglyceride, and liver glycogen in CAR-induced rats were presented in [Table 2]. The normal blood glucose level was found to be 79.19 mg%. There was an increase in the blood glucose levels of rats exposed to CAR (group II) (P < 0.05). Quetiapine (30 mg/kg p.o. for 21 days) produced a significant (P < 0.01) rise in the blood glucose level in the CAR-induced rats (group III) when compared with normal control (group I) and pathogenic control (group II). Rosuvastatin (10 and 20 mg/kg p.o.) and CDP-choline (100 mg/kg p.o.) did not affect the blood glucose levels (groups IV, V, and VI). Rosuvastatin 10 and 20 mg/kg p.o. and CDP-choline 100 mg/kg p.o. produced significant (P < 0.01) reduction of quetiapine induced rise in blood glucose levels (groups VII, VIII, and IX).
Table 2: Effect of quetiapine, rosuvastatin, and quetiapine with CDP-choline alone and in combination on different parameters in CAR-induced rats

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The normal triglyceride level was found to be 70.99 mg%. There was an increase in the triglyceride levels of rats exposed to CAR (group II) (P < 0.05). Rosuvastatin and CDP-choline did not produce significant changes in the levels of triglycerides in CAR-induced rats (groups IV, V, and VI). However, rosuvastatin and CDP-choline produced significant (P < 0.01) reduction of quetiapine induced rise in serum triglycerides levels (groups VII, VIII, and IX).

After induction of CAR for 7 days in rats, no significant (P > 0.05) change in the liver glycogen level was observed when compared with the vehicle control group. Treatment with quetiapine (30 mg/kg, group III) resulted in a no significant (P > 0.05) change in the liver glycogen levels compared to the normal control (group I) and pathogenic control (group II). Rosuvastatin 10 and 20 mg/kg p.o. caused reduction in liver glycogen levels (groups IV and V). CDP-choline 100 mg/kg p.o. had no significant effect on the level of liver glycogen in CAR-induced rats (group VI). Rosuvastatin and CDP-choline did not produce significant changes in the levels of liver glycogen in CAR-induced rats (groups VII, VIII, and IX).

In the present study, it was observed that after induction of CAR in rats for 21 days, the fasting glucose and triglyceride level were considerably increased as compared to normal rats, suggesting that induction of CAR itself can lead to metabolic syndrome. Similar observation was reported earlier. [7] There was a significant rise in blood glucose level in rats treated with quetiapine, 30 mg/kg (group III). This rise in blood glucose and triglyceride level in this group III implies that quetiapine aggravate the metabolic syndrome induced by CAR. The nonsignificant per se effect of rosuvastatin (10 and 20 mg/kg) and CDP-choline (100 mg/kg) on glucose level of CAR-induced rats reveals that rosuvastatin and CDP-choline did not aggravate metabolic syndrome. However, the reduction of quetiapine induced rise in glucose and TG levels by rosuvastatin and CDP-choline reveals that these drugs could attenuate the metabolic syndrome caused by quetiapine. The nonsignificant changes in the liver glycogen level of CAR-induced rats and quetiapine-treated rats indicate that liver plays a minor role in the metabolic syndrome caused by CAR or quetiapine. The reduction of glycogen levels caused by rosuvastatin reveals that statins have mild adverse affect on liver glycogen storage capacity. However, the nonsignificant effect of CDP-choline on liver glycogen reveals that CDP-choline did not produce adverse effects on liver function. The nonsignificant effects of rosuvastatin and CDP-choline on liver glycogen levels of quetiapine-treated CAR-induced rats further confirm that these two drugs attenuate. Study concluded that rosuvastatin and CDP-choline could decrease the metabolic syndrome caused by quetiapine and CAR. It was observed that after induction of CAR in rats for 7 days, the fasting glucose level was considerably increased as compared to fasting blood glucose level of normal rats, suggesting that schizophrenia itself can lead to glucose imbalance.

 
   References Top

1.Yumru M, Savas HA, Kurt E, Kaya MC, Selek S, Savas E, et al. Atypical antipsychotics related metabolic syndrome in bipolar patients. J Affect Disord 2007;98:247-52.  Back to cited text no. 1
    
2.Basu R, Brar JS, Chengappa KN, John V, Parepally H, Gershon S, et al. The prevelance of the metabolic syndrome in patients with shizoaffective disorder bipolar subtype. Bipolar Disord 2004;6:314-8.  Back to cited text no. 2
    
3.Fagiolini A, Frank E, Houck PR, Mallinger AG, Swartz HA, Buysse DJ, et al. Prevalence of obesity and weight changes during treatment in patients with bipolar disorder. J Clin Psychiatry 2002;160:112-7.  Back to cited text no. 3
    
4.Haupt DW, Newcomer JW. Abnormalities in glucose regulation associated with mental illness and treatment. J Psychosom Res 2002;53:925-33.  Back to cited text no. 4
    
5.Newcomer JW. Second generation (atypical) antipsychotics and metabolic effects: A comprehensive literature review. CNS Drugs 2000;19:1-93.  Back to cited text no. 5
    
6.Parasuraman S, Raveendran R, Kesavan R. Blood sample collection in small laboratory animals. J Pharmacol Pharmacother 2010;1:87-93.  Back to cited text no. 6
[PUBMED]  Medknow Journal  
7.Dwyer DS, Donohoe D. Induction of hyperglycemia in mice with atypical antipsychotic drugs that inhibit glucose uptake. Pharmacol Biochem Behav 2003;75:255-60.  Back to cited text no. 7
    



 
 
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