Predictive Validity of Some Common Animal Models of Bipolar Disorder Using Lithium and Lamotrigine Therapy: An Attempt towards a Battery-Based Approach for the Evaluation of Mood Stabilizers

OBJECTIVE: To determine the predictive validity of some of the commonly employed models of mania and depression using standard drugs i.e. lithium (70 mg/kg) and lamotrigine (5 mg/kg) in male Wistar rats. METHODS: The depression facet of bipolar disorder was evaluated using forced swim test, tail suspension test, and chronic mild stress test. The models used to evaluate the mania facet of bipolar disorder were isolation-induced aggression test, saccharine preference test, and morphine-sensitized hyperlocomotion test. RESULTS: The immobility time was significantly (p<0.05) reduced by lamotrigine in the tail suspension test and the forced swim test, while lithium caused significant (p<0.05) reduction only in the tail suspension test. Rats exposed to chronic mild stress showed the maximal increment of 1% sucrose consumption at the 3rd week of treatment in both the lithium (p<0.001) and lamotrigine (p<0.01) groups. In the isolation-induced aggression test, the aggressive behaviour of rats was significantly reduced by both lithium [approach (p<0.001), attack (p<0.01), and bite (p<0.01)] and lamotrigine [approach (p<0.001), and attack (p<0.05)]. Neither of the drugs were effective in the saccharine preference test. Only lithium was able to significantly (p<0.05) reduce the crossing parameter in morphine-sensitized rats. CONCLUSION: Our study identifies the chronic mild stress test and isolation-induced aggression test of having the highest predictive validity in the depression and mania facets of bipolar disorder, respectively, and should be a part of a battery of tests used to evaluate novel mood stabilizers.

Hypolipidaemic and anti-inflammatory effects of fixed dose combination of atorvastatin plus ezetimibe in Indian patients with dyslipidaemia

<p><b>INTRODUCTION</b>We aimed to assess the efficacy of fixed dose combination of atorvastatin plus ezetimibe in Indian patients with dyslipidaemia.</p><p><b>METHODS</b>A double-blind study was conducted to assess the effect of fixed dose combination of ezetimibe 10 mg plus atorvastatin 10 mg on lipid profile, oxidised low-density lipoprotein (ox-LDL), high-sensitivity C-reactive protein (hsCRP) and soluble intercellular cell adhesion molecule (sICAM) in dyslipidaemic patients with or at high risk of coronary artery disease, and compare it with atorvastatin 10 mg monotherapy. 30 patients were randomised to receive ezetimibe plus atorvastatin or atorvastatin once daily for four weeks.</p><p><b>RESULTS</b>Of the 30 patients, 10 men and 5 women (mean age 54.3 ± 1.6 years) received ezetimibe plus atorvastatin, while 13 men and 2 women (mean age 53.7 ± 2.8 years) received only atorvastatin. The combination treatment significantly reduced total cholesterol (percentage treatment difference -14.4 ± 6.5, 95% confidence interval [CI] -1.0 to -27.7; p = 0.041) and LDL cholesterol (LDL-C; percentage treatment difference -19.9 ± 6.1, 95% CI -7.4 to -32.4; p = 0.003) compared to atorvastatin monotherapy. 13 patients on combination treament achieved the National Cholesterol Education Program target for LDL-C as compared to 9 patients on atorvastatin monotherapy (p = 0.032). Significant reductions in very low-density lipoprotein cholesterol, triglyceride, ox-LDL and sICAM were observed with combination treatment compared to atorvastatin monotherapy. However, no significant change was seen in high-density lipoprotein cholesterol or hsCRP levels between the two groups.</p><p><b>CONCLUSION</b>Combination treatment with atorvastatin and ezetimibe had relatively better lipid-lowering and anti-inflammatory efficacy than atorvastatin monotherapy.</p>