[ possible interaction of dopamine system in nucleus accumbens shell and glutamate system of prelimbic region on locomotor activity in rat]

Nucleus accumbens [NAc] and prefrontal cortex [PFC] dopaminergic and glutamatergic systems are involved in regulating of locomotor activity behaviors. This study has investigated the interaction of NAc shell dopaminergic system and prelimbic glutamatergic systems in regulating locomotor activity and related parameters. The aim of this study was the effect the drugs injection interaction in the brain of male Wistar rats on locomotor activity and related parameters, in the order of this purpose, open field apparatus that automatically recorded locomotor activity was employed. Unilateral intra-cerebral injection of drugs was done. Unilateral intra-prelimbic injection of D-AP7 [N-methyl-D-aspartic acid=NMDA receptor antagonist; 0.25, 0.5 and 1micro g/micro l] did not alter locomotor activity behaviors. However, infusion of NMDA [0.9micro g/micro l] in this region increased locomotor activity [P<0.01], whereas decreased rearing [P<0.01] and grooming [P<0.01] which was blocked by D-AP7 [0.25micro g/micro l] [P<0.01]. Moreover, unilateral infusion of SCH23390 [dopamine D1 receptor antagonist; 0.25, 0.5 and 1micro g/micro l] into the left NAc shell did not alter locomotor activity. However, injection of SKF38393 [dopamine D1 receptor agonist; 4micro g/micro l] into the left NAc shell increased locomotor activity [P<0.05] which was blocked by SCH23390 [0.25micro g/micro l] [P<0.01]. Furthermore, the subthreshold dose infusion of SCH23390 [0.25micro g/micro l] into the left NAc shell reduced the effect of intra-prelimbic NMDA on locomotor activity [P<0.01]. In addition, intra-NAc shell administration of the subthreshold dose of SKF38393 [1micro g/micro l] potentiated the middle dose [P<0.05], whereas decreased the higher dose of intra-left prelimbic NMDA response [P<0.05] on locomotor activity. The results suggested a modulatory effect of the NAc shell dopaminergic system on increased locomotor activity by activating glutamate system in prelimbic.

effect of cholestasis on rewarding and exploratory behaviors induced by opioidergic and dopaminergic agents in mice

Several investigations have indicated that cholestasis decreases opioid receptor expression in the brain following increased opioidergic neurotransmission. The opioidergic system plays an important role in regulation of reward circuits that may be produced via dopamine-dependent mechanisms. It has been suggested that the dopaminergic system of the nucleus accumbens is necessary in conditioned place preference [CPP]. The aim of this study is, therefore, to test if cholestasis can alter the reward system and the involvement of opioidergic and dopaminergic systems in this phenomenon. We used CPP and hole-board paradigms to measure the reward effect and exploratory behaviors, respectively, in mice. Cholestasis was induced by ligation of the main bile duct, using two ligatures and transecting the duct between them [BDL mice]. The data showed that morphine [1 and 2 mg/kg], sulpiride [80 mg/kg] and SKF38393 [20 mg/kg] produced CPP, while naloxone [1 mg/kg] and SCH23390 [1 mg/kg] produced conditioned place aversion [CPA], whereas quinpirole had no effect in sham-operated mice. However, morphine [2 mg/kg, i.p.], sulpiride [40 mg/kg] and SKF38393 [10 mg/kg] induced CPP in BDL mice compared to sham-operated mice. Naloxone- or SCH23390-induced CPA was reduced in BDL mice compared with the respective sham-operated mice. Quinpirole tended to induce aversion in BDL mice which was, however, not significant. In addition, quinpirole 1 mg/kg] and SCH23390 [1 mg/kg] increased head-dip exploratory behavior, whereas naloxone [2 mg/kg] caused a decrease in head-dip exploratory behavior in sham-operated mice. Morphine [2 mg/kg], SCH23390 [1 mg/kg] and quinpirole [0.25 and 0.5 mg/kg] induced anxiogenic-like behavior in BDL mice. It can be concluded that cholestasis differentially alters the reward effects of opioidergic and dopaminergic agents

[Molecular analysis of mutation MEFV gene involved inpatient's with familial of Mediterranean fever referred to Taleghani hospital Tehran between 2006-2008]

Familial Mediterranean fever [FMF] is an autosomal recessive disorder characterized by recurrent attacks of fever and inflammation in the peritoneum, synovium, or pleura, accompanied by pain. In this study, we examined all 10 exons to determine the most common mutations in MEFV gene as a single gene associated with FMF. In this basic study, 51 clinically diagnosed Iranian FMF patients referred to Taleghani hospital were studied. Peripheral blood was gained from them and genomic DNA was extracted according to phenol chloroform standard protocol. They were screened for the MEFV mutation using bidirectional sequencing and finally, the sequences were analyzed by related soft wares. Of 51 patients suspected to FMF, 24 [47.05%] were positive for mutation and 27 [52.95%] had no mutations. 14 patients had M694V mutation in exon10 including 4 homozygote mutation, 8 heterozygote and 4 compound heterozygote. Moreover, we could find 6 patients with M680I mutation and 2 individual [8.3%] with V721I mutation in exon 10. Only one person carried E148Q heterozygote mutation in exon 2. Our finding were compatible with others investigation that M694V mutation is the most common mutation in different populations

[Nucleophosmin gene mutations in acute myeloid leukemia]

Heterozygous mutation of the nucleophosmin gene [NPM1] has recently been described as one of the most frequent genetic lesions in acute myeloid leukemia [AML]. NPM1 gene mutations tend to occur more frequently in women, and also tend to be associated with a higher white blood cell count. There is no significant age difference. NPM1-mutated AML is preferentially associated with AML monocytic differentiation [in particular FAB M5b], lack of CD34, normal cytogenetics, FLT3 gene mutations, and a trend toward favorable clinical outcome, specially in patients without FLT3 gene mutation. NPM1 gene mutations cause a framshift in the C-terminus of exon 12, disrupting the NPM nucleolar-localization signal or generating leucin-rich nuclear export motif, resulting in abnormal cytoplasmic accumulation of NPM. Detection of NPM1 gene mutation may allow dissection of the heterogeneous group of AML with normal karyotype into prognostically different subgroups. Exploring the mechanisms may lead to a better understanding of how mutant NPM protein becomes leukemogenic, thereby providing insights for the development of new chemotherapeutic agents