The addiction potential of abused drugs can be different although their pharmacodynamics characteristics are quite similar.In this article, the influence of pharmacokinetics characteristics of a drug on its addiction potential was discussed. A more rapid rate of onset had been shown to result in greater propensity to addiction. Although prolonging the duration of action could reduce the responding rate in animal self-administration experiments, it might not influence the strength of a drug. Understanding the relationship between the pharmacokinetics characteristics and addiction potential may contribute to the rational use and development of these kinds of drugs.

ORL1(Opioid receptor-like 1)receptor and its endogenous ligand,nociceptin/orphanin FQ,belong to G protein-coupled receptor super family with multiple functions.ORL1 is not only endowed with anti-opioid properties(it suppresses opioid-mediated analgesia),but also involved in cognitive processes,emotion,cardioprotection and neuroendocrine secretion.The research on ORL1 and N/OFQ will certainly be helpful to develop new therapeutic drugs and to find drug targets of clinical application.

Objective: To explore value of 6-minute walking in rehabilitation therapy of patients with chronic heart failure (CHF). Methods: A total of 78 CHF patients were selected from department of geriatrics of our hospital. They were randomly and equally divided into 6min walking test (6MWT) group (received 6-min walking training based on routine treatment, twice/d) and routine treatment group. After six weeks, 6min walking distance (6MWD), heart rate and left ventricular ejection fraction (LVEF) were compared between two groups before and after treatment. Results: After six weeks, there were significant improvements in related indexes in both groups, P<0.05 all; compared with routine treatment group, there were significant increase in 6MWD [(307.6±39.3) m vs. (503.4±44.4) m] and LVEF [(45.3±17.9) % vs. (58.7±19.2) %], and significant decrease in heart rate of recovery period after 6MWT [(73.3±2.9) times/min vs. (65.7±2.1) times/min] in 6MWT group, P<0.05 all. Conclusion: Six-minute walking can significantly improve symptoms of heart failure and enhance exercise tolerance, and it possesses important value for recovery of heart function in these patients.

Objective To investigate rats reared in social isolation as a model of behavioral symptoms of neurodevelop-mental psychiatric disorders including schizophrenia.Methods Male rat pups were housed in individual cages from post-weaning to adulthood.Locomotor activity detection, Morris water maze test and social interaction test were performed. Results Compared with controls, the social isolation-reared rats got more body mass, showed locomotor hyperactivity and increased social interaction, but significant spatial learning changes were not observed in Morris water maze test.Conclu-sion Exposing rats to social isolation can profoundly affect behavior in adulthood, which can be used to build animal mod-els of neurodevelopmental psychiatric disorders including schizophrenia.

Down-regulation of adult hippocampal neurogenesis has been regarded as one of the important biological and cellular basis of depression. Recent studies have shown that there is a close correlation between neurogenesis and angiogenesis. Several angiogenesis factors, especially vascular endothelial growth factor (VEGF), play a vital role on angiogenesis. They not only have the neurotrophic and neuroprotective effects, but also up-regulate hippocampal neurogenesis. Thus,VEGF may be involved in the occurrence and treatment of major depression. This article reviews current understanding of the relationship between adult brain angiogenesis and depression.

The C-terminal tail of opioid receptor is important for opioid receptor phosphorylation,desensitization and internalization after opioid agonists treatment.The C-terminal point mutant and truncated mutant of amino acid residues of ?opioid receptors such as T394A,T383A,T357A,S355A affect the function of the opioid receptor obviously.The identical results could be seen in the C-terminal point mutant S363A of ?opioid receptor and S369A of ?opioid receptor.It is well known that opioid receptor requires interaction with other proteins for function,regulation and trafficking.Although proteins such as PPL,FilaminA,PLD2,PKCI,GASP and EBP50/NHERF have been identified to interact with C-terminals of opioid receptors,the role of interaction of these proteins with opioid receptor in the dependence,tolerance and addiction of opioids is dubious.Therefore,looking for the proteins specifically interacting with the C-terminals of opioid receptor may be important to understand the mechanism of opioids addiction.

Opioid peptides and their receptors play an important r ole in the pathophysiologic process of stroke. The concentration of endogenous o pioid peptides elevates, while the density of opioid receptors decreases in CNS during cerebral ischemia; on the other hand, opioids influence the development o f stroke through regulating the contraction of cerebral vessel, immuno-endocrin e system and neuroprotection against injury. Thus, drugs that regulate the opioi d system may be a new therapeutic approach for prevention and treatment of cereb ral ischemia.

In recent years, the importance of tyrosine phosphorylation in the nervous system of mammalian is gaining recognition. Tyros ine protein kinases exert important modulatory effect on the proliferation, diff erentiation, migration and metabolism-related singal transduction pathways in c ells. In this paper we reviewed the signal cascade process of three different ty rosine protein kinase families, including Trk, Src and Eph tyrosine protein kina se families. Furthermore, we discussed important role and possible mechanisms of these tyrosine protein kinases on the neuron synapse plasticity and learning an d memory process.

Two types of cannabinoid receptors,named cannabinoid receptor 1(CB1) and cannabinoid receptor 2(CB2),have been cloned.CB2 receptors are expressed predominantly in the peripheral immune tissues,but accumulating evidence has revealed that CB2 receptors are also expressed in CNS.Previous studies showed that CB2 agonists can cure and suppress formation of inflammatory and neurophathic pain without central effects after chronic administration.Therefore,they will have good clinical applications in the treatment of pain and neurodegenerative diseases.In this paper,we will review the tissue distribution of CB2 in CNS and pharmacological characteristics of the CB2 agonists have been reviewed.

The homeostasis of extracellular glutamate concentration is critically regulated by glutamate transporters(GTs).Malfunction or decreased expression of GTs has been implicated in the pathogenesis of various nervous system diseases.And among the GTs,glutamate transporter 1(GLT-1)plays a critical role as "glutamate pump".Recent research also finds some GLT-1 variants which alternate C-terminal splicings.Altered expression of proteins encoded by splice variants of GLT-1 has been noted in a number of disease states.Maintaining a physiological range of extracellular glutamate through regulating GTs expression or function may improve some pathological conditions.Many drugs are reported that can regulate GTs.For example,ceftriaxone,phencyclidine,citicoline,riluzole,AKT,thrombosin can up-regulate the expression or function of glutamate transporters;etomidate,clozapine,aspartic acid analogs,endothelin can down-regulate the expression or function of glutamate transporters.In this paper,the drugs which effect GTs will be summarized in order to provide a new insight into the drug design and clinical treatment of neurological diseases.