对恶性肿瘤性别差异的再认识

恶性肿瘤性别差异表现在发病率、预后、治疗等多方面。生理结构、生活方式、工作、性格等流行病学因素是造成恶性肿瘤性别差异的外因,性激素及其受体研究在一定程度上解释了性别差异的本质,且为恶性肿瘤的内分泌治疗提供了理论依据。随着分子生物学技术发展,基因多态、分子突变等深入研究成果揭示更深层次的原因。     

Emotionally controlled decision-making and a gene variant related to serotonin synthesis in women with borderline personality disorder

The Iowa Gambling Task (IGT) was used to examine (i) social decision-making in women with borderline personality disorder (BPD), and (ii) the relationship between impaired decision-making and the tryptophan hydroxylase-1 (TPH-1) gene, involved in serotonin synthesis. Forty-two women with BPD and a history of suicide attempts were genotyped, and the frequency of a TPH-1 haplotype previously uniquely associated with BPD was calculated. The BPD group scored significantly lower than a control group in the IGT. Furthermore, the TPH-1 haplotype displayed a significantly higher frequency in BPD participants with impaired decision making, compared to BPD participants with normal scores. These findings suggest that impaired decision-making as determined by the IGT is a feature of BPD and may be (i) associated with serotonin dysfunction, and (ii) possibly relevant for suicidal behavior.     

d-Serine facilitates the effects of extinction to reduce cocaine-primed reinstatement of drug-seeking behavior

Male Sprague Dawley rats were allowed to self-administer cocaine (0.5 mg/kg) during 90 min sessions for a period of 15 days. On day 16, rats were either held abstinent in their home cage environment or experienced an extinction session in which the active lever had no programmed consequences. Facilitating N-methyl-d-aspartate (NMDA) receptor activity with the coagonist d-serine (100 mg/kg i.p.) before or following the extinction session significantly reduced the subsequent cocaine-primed reinstatement of drug-seeking behavior tested on day 17. d-Serine significantly reduced drug-primed reinstatement only when combined with extinction, and its effectiveness when administered following the training session suggested that an enhancement of consolidation of extinction learning had occurred. In contrast, d-serine treatment did not reduce sucrose-primed reinstatement, indicating that the beneficial effects of this adjunct pharmacotherapy with extinction training were specific to an addictive substance (cocaine) and did not generalize to a natural reward (sucrose).     

The medial amygdala: Serotonergic inhibition of shock-lnduced aggression and pain sensitivity in rats

Two aspects of the amygdaloid complex (corticomedial and basolateral) were examined with reference to serotonergic inhibition of shock-induced aggression. Fighting was significantly depressed by serotonergic stimulation (5-HT, 10 μg bilateral) in the corticomedial amygdala while serotonergic blockade (methysergide, 5 μg bilateral) in this region increased levels of fighting. No consistent effects were obtained with serotonergic manipulation of the basolateral amygdala. Further investigation revealed that the state of serotonergic activity in medial amygdaloid sites was associated with concomitant alterations in the animals' sensitivity to footshock. Results are discussed in relation to a) a general inhibitory role of serotonin in behavioural mechanisms and b) a dopaminergic-serotonergic balance for behavioural arousal involving medial amygdaloid nuclei.     

Activation of adenosine receptors in the posterior cingulate cortex impairs memory retrieval in the rat

Adenosine A1 and A2A receptor agonists and antagonists have been reported to alter learning and memory. The aim of our study was to investigate the involvement of adenosinergic system in memory retrieval into posterior cingulate cortex (PCC) of Wistar rats. To clarify this question, we tested specifics agonist and antagonists of adenosine A1 and A2A receptors in rats submitted to a one-trial inhibitory avoidance task. The stimulation of adenosine A1 and A2A receptors by CPA and CGS21680, respectively, impaired memory retrieval for inhibitory avoidance task, into PCC. These findings provide behavioral evidence for the role of adenosinergic system in the memory retrieval into PCC.     

Non-ligand activation of estrous behavior in rodents: cross-talk at the progesterone receptor

Estrous behavior in rodents is triggered by the binding of progesterone (P) to its intracellular receptor (PR). Non-steroidal agents (i.e., gonadotropin-releasing hormone, noradrenaline, dopamine and others), acting at the membrane, can facilitate estrous behavior in estrogen-primed rats. This action is mediated through the generation of second messengers (cyclic AMP, cyclic GMP, calcium) which, in turn, phosphorylate through diverse kinase systems (protein kinases A, G or C) either the PR or associated effector proteins linking the PR to the trans-activation machinery. P or its metabolites also activate cyclic AMP-signaling pathways by acting directly on the membrane or by modulating neurotransmitter release. Molecular processes resulting from second messenger signaling pathways and those from the progesterone-RP interaction synergize to elicit a full behavioral response.     

人是怎样与世界统一的——一个关于细胞信息跨膜传递特异性的假说

本文在讨论有限和无限的对立统一规律在抗原和抗体产生机制中的体现的基础上,提出关于细胞信息跨膜传递特异性机制的假说：第一信使可能由有限的基本单位构成,其信息的特异性可能通过有限的信息中介的组合来得以体现,效应部位也可能因具有特定的信息中介结合位点的组合而产生特异的细胞效应。本文最后为这一假说的证实提出展望。     

Effects of fluoxetine on play dominance in juvenile rats

In a series of three studies, we investigated the influence of a selective serotonin re-uptake inhibitor (fluoxetine) on the rough-and-tumble play of juvenile rats. In Experiment 1, both members of eight pairs of solitary-housed juvenile rats received either vehicle, 2.5, 5, or 10 mg/kg fluoxetine in a counterbalanced within-subject design 20 min before being allowed to play for 5 min periods on four successive test days. The 5 and 10 mg/kg pretreatments significantly reduced incidence of pins during play without affecting dorsal contacts. In Experiment 2, one member of each of 19 established play pairs received 5 mg/kg fluoxetine 20 min before play, while the other member received vehicle. Dominant rats showed no reduction in pins as a result of fluoxetine treatment, but subordinate rats who received fluoxetine exhibited significant reductions in pins. Subsequent dyadic analyses indicated that in pairs where the subordinate animal received fluoxetine, dominant animals maintained their pinning advantage over the 10 days of testing, but in pairs where the dominant animals received fluoxetine, this pinning asymmetry diminished. In Experiment 3, we replicated the above procedure with inexperienced play pairs, to control for the effects of prior social learning. Fluoxetine treatment (5 mg/kg) significantly reduced both pins and dorsal contacts in all treated rats. The results indicate that fluoxetine can reduce the playful pins of juvenile rats, but that prior social learning mediates the strength of these effects. © 1996 Wiley-Liss, Inc.     

Differential Effect of TEA on Long-Term Synaptic Modification in Hippocampal CA1 and Dentate Gyrus in vitro

The effectiveness of tetraethylammonium (TEA) and high-frequency stimulation (HFS) in inducing long-term synaptic modification is compared in CA1 and dentate gyrus (DG) in vitro. High-frequency stimulation induces long-term potentiation (LTP) at synapses of both perforant path-DG granule cell and Schaffer collateral-CA1 pyramidal cell pathways. By contrast, TEA (25 mM) induces long-term depression in DG while inducing LTP in CA1. The mechanisms underlying the differential effect of TEA in CA1 and DG were investigated. It was observed that T-type voltage-dependent calcium channel (VDCC) blocker, Ni²⁺ (50 μM), partially blocked TEA-induced LTP in CA1. A complete blockade of the TEA-induced LTP occurred when Ni²⁺ was applied together with the NMDA receptor antagonist, D-APV. The L-type VDCC blocker, nifidipine (20 μM), had no effect on CA1 TEA-induced LTP. In DG of the same slice, TEA actually induced long-term depression (LTD) instead of LTP, an effect that was blocked by D-APV. Neither T-type nor L-type VDCC blockade could prevent this LTD. When the calcium concentration in the perfusion medium was increased, TEA induced a weak LTP in DG that was blocked by Ni²⁺. During exposure to TEA, the magnitude of field EPSPs was increased in both CA1 and DG, but the increase was substantially greater in CA1. Tetraethylammonium application also was associated with a large, late EPSP component in CA1 that persisted even after severing the connections between CA3 and CA1. All of the TEA effects in CA1, however, were dramatically reduced by Ni²⁺. The results of this study indicate that TEA indirectly acts via both T-type VDCCs and NMDA receptors in CA1 and, as a consequence, induces LTP. By contrast, TEA indirectly acts via only NMDA receptors in DG and results in LTD. The results raise the possibility of a major synaptic difference in the density and/or distribution of T-type VDCCs and NMDA receptors in CA1 and DG of the rat hippocampus.