European journal of pharmacology
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In the present study, the effects of bilateral intra-dorsal hippocampal (intra-CA1) injections of α2-adrenoceptor agonist and antagonist, on muscimol state-dependent memory were examined in mice. A single-trial step-down passive avoidance task was used for the assessment of memory retention in adult male NMRI mice. Administration of muscimol (0.1 μg/mouse, intra-CA1) 15 min before training or testing induced impairment of memory retention. ⋯ Pre-test intra-CA1 administration of certain doses of yohimbine (0.25 and 0.5 μg/mouse), doses which were ineffective when given alone, improved pre-training muscimol (0.1 μg/mouse)-induced retrieval impairment. Moreover, pre-test co-administration of yohimbine (0.25 and 0.5 μg/mouse, intra-CA1) and muscimol (0.025 μg/mouse, intra-CA1), an ineffective dose, significantly restored the retrieval and induced muscimol state-dependent memory. It may be concluded that the α2-adrenoceptors of the dorsal hippocampal area play an important role in muscimol state-dependent memory.
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The aim of this study was to determine the frequencies of SNPs in the vitamin K epoxide reductase complex subunit 1 (VKORC1) and cytochrome P450 2C9 (CYP2C9) genes and their effect on warfarin dose requirement, over anticoagulation and other adverse outcomes in Indian population. A total of 145 warfarin treated patients for various clinical conditions were screened for VKORC1 and CYP2C9 gene polymorphisms by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. We found that homozygous VKORC1-1639 AA and CYP2C9 (*)3/(*)3 polymorphisms showed 100% association with risk of over anticoagulation and other adverse events. ⋯ A drastic variation from other Asian countries was observed in Indian population with regard to the distribution of different VKORC1 -1639 genotypes. Our results suggest that both VKORC1 and CYP2C9 genotypes showed significant impact on warfarin dose requirement, over anticoagulation in the first month of anticoagulation and number of bleeding episodes. The variation in therapeutic dosage of warfarin and the associated adverse events across different populations is due to the wide differences in the frequency of these warfarin sensitive alleles.