OBJECTIVE Alcoholism is one of the most damaging psychiatric disorders and causes serious social and health problems in the world. However,there are no ideal treatments for this disease in clinic.Phosphodiesterases(PD...OBJECTIVE Alcoholism is one of the most damaging psychiatric disorders and causes serious social and health problems in the world. However,there are no ideal treatments for this disease in clinic.Phosphodiesterases(PDEs) are a superfamily of enzymes consisting of 11 PDE families that hydrolyze cyclicAMP(cA MP) and/or cyclicGMP(cGMP). Among them,PDE4 is critical in the control of intracellular cAMP levels and has been shown to play an important role in the regulation of ethanol consumption.However,the functional role of PDE4 in mediating alcoholism remains unclear. METHODS Ethanol drinking and preference were examined using the two-bottle choice and/or drinking-in-dark(DID) test in high alcohol preferring(HAP) animals,including C57,HAP,and PDE4-subtype knockout mice,and Fawn-Hooded(FH/Wjd) rats,treated with or without the PDE4 inhibitor rolipram or roflumilast. Ethanol withdrawal-induced anxiety-and depressive-like behaviors were examined using the elevated plusmaze,holeboard,forced-swim,and tail-suspension tests in C57 mice or FH rats in the presence of PDE4 inhibition. Levels of cAMP,CREB were determined in brain regions. RESULTS Treatment with rolipram or roflumilast decreased ethanol intake and preference in two-bottle choice and DID tests in C57 and HAP mice as well as FH rats. Mice deficient in PDE4 B,but not PDE4 D,displayed similar effects to general PDE4 inhibition. In addition,rolipram reversed ethanol withdrawal-induced anxietyand depressive-like behaviors 1 d and 14 d,respectively,following withdrawal from ethanol drinking in the two-bottle choice in C57 mice or FH rats. Locomotor activity was not changed in either mice or rats treated with the PDE4 inhibitors. Levels of cAMP,p CREB in the brain were increased by rolipram.CONCLUSION The results provide solid evidence for the important role of PDE4 in ethanol consumptionand ethanol withdrawal-induced symptoms. Inhibitors of PDE4,in particular the PDE4 B isoform,can be a novel class of treatment for alcoholism.展开更多
Great variability exists in the response to painful experimental stimuli, in the pain experienced between individuals with similar injuries, in the susceptibility to chronic pain, and in the response to analgesic trea...Great variability exists in the response to painful experimental stimuli, in the pain experienced between individuals with similar injuries, in the susceptibility to chronic pain, and in the response to analgesic treatments. Genetic factors account for a significant proportion of the variability, but have only recently been systematically studied. Comprehensive surveys of the sensitivity of inbred mouse strains demonstrate the remarkable heritability展开更多
OBJECTIVE Individuals vary in sensitivity to the behavioral effects of nicotine,resulting in differences in their vulnerability to addiction.The role of rearing environment in determining individual sensitivity to nic...OBJECTIVE Individuals vary in sensitivity to the behavioral effects of nicotine,resulting in differences in their vulnerability to addiction.The role of rearing environment in determining individual sensitivity to nicotine is unclear.The neuropharmacological mechanisms mediating the effect of rearing environment on the actions of nicotine are also understood.Thus,the contribution of rearing environment in determining the sensitivity to the locomotor effects of nicotine and regulating α4β2*-and α7-nicotinic acetylcholine(n ACh) receptor expressionwas determined in rats reared in isolated(IC) or enriched(EC) conditions.METHODS To measure locomotor activity,adolescent rats(postnatal day 21-51)were injected with saline(1 mL·kg^(-1)) or nicotine(0.3 mg·kg^(-1)) subcutaneously,then placed in chamberswhere ambulatory activity was monitored for 30-min by computer for 14 daily sessions.α4β2*-andα7-n ACh receptor expression in the mesolimbic dopamine pathway was determined by quantitative autoradiography of [125 I]-epibatidine and [125 I]-bungarotoxinbinding,respectively,in 16 μmol·L^(-1) coronal sections.Values for receptor expression in fmol are ±s of 8 brains and compared by two-tailed,unpaired t-test with P<0.05 considered significant.RESULTS EC-rats are similarly sensitive as IC-rats to the locomotor effects of nicotine.[125 I]-epibatidine binding in the ventral tegmental area of EC-rats was reduced(2.8±0.3 fmo L) compared to IC-rats(4.0±0.4 fmo L);there was no difference in the nucleus accumbens.There was no difference between EC-and IC-rats in α7-n ACh receptor expression in the mesolimbic dopamine pathway.CONCLUSION Rearing environment differentially regulates n ACh receptor subtypes in EC and IC rats.These data suggest regulation of n ACh receptors by environmental factors may be a mechanism for the protective effect of enrichment against altered sensitivity to nicotine in genetically vulnerable individuals.The characterization of these mechanisms will aid in development of novel pharmacological tools mimicking the protection afforded by environmental enrichment in nicotine-sensitive individuals.展开更多
The central purpose of this paper is to explain how Darwin′s theory of evolution by natural selection can be used in understanding current human behaviour. First, Darwin′s logic is briefly described. Development is ...The central purpose of this paper is to explain how Darwin′s theory of evolution by natural selection can be used in understanding current human behaviour. First, Darwin′s logic is briefly described. Development is an important issue when applying evolutionary theory to human behaviour. The notion of innate developmental organization of psychological mechanisms is introduced. The possible social and political outcomes produced when different levels of innate developmental organization are paired with different beliefs about it are considered. The notion of psychological mechanisms as evolved adaptations is considered in some detail. Then I discuss different ways evolutionists think about how genes are involved in the development of adaptations. The paper concludes with a framework for considering how ancestral adaptations function in current environments and outlines some ways of studying them. In China and many other parts of the world people desire a more harmonious society. I hope that this paper will be of some small help in achieving this great task.展开更多
Occupational Health Psychology(OHP)is an interdisciplinary field concerned with psychological factors in employee's health,safety,and well-being,closely related to Industrial/Organizational(I/O)Psychology. Specifi...Occupational Health Psychology(OHP)is an interdisciplinary field concerned with psychological factors in employee's health,safety,and well-being,closely related to Industrial/Organizational(I/O)Psychology. Specific areas of concern are accidents,injuries,illness,stress,violence,counterproductive work behavior,and work-family conflict. Based on his research,Dr. Paul E. Spector answered our questions on aspects of Occupational Health Psychology,Cross-cultural Psychology and research/statistical methods in I/O Psychology. His opinions or suggestions about future research in I/O Psychology are informative and inspiring.展开更多
文摘OBJECTIVE Alcoholism is one of the most damaging psychiatric disorders and causes serious social and health problems in the world. However,there are no ideal treatments for this disease in clinic.Phosphodiesterases(PDEs) are a superfamily of enzymes consisting of 11 PDE families that hydrolyze cyclicAMP(cA MP) and/or cyclicGMP(cGMP). Among them,PDE4 is critical in the control of intracellular cAMP levels and has been shown to play an important role in the regulation of ethanol consumption.However,the functional role of PDE4 in mediating alcoholism remains unclear. METHODS Ethanol drinking and preference were examined using the two-bottle choice and/or drinking-in-dark(DID) test in high alcohol preferring(HAP) animals,including C57,HAP,and PDE4-subtype knockout mice,and Fawn-Hooded(FH/Wjd) rats,treated with or without the PDE4 inhibitor rolipram or roflumilast. Ethanol withdrawal-induced anxiety-and depressive-like behaviors were examined using the elevated plusmaze,holeboard,forced-swim,and tail-suspension tests in C57 mice or FH rats in the presence of PDE4 inhibition. Levels of cAMP,CREB were determined in brain regions. RESULTS Treatment with rolipram or roflumilast decreased ethanol intake and preference in two-bottle choice and DID tests in C57 and HAP mice as well as FH rats. Mice deficient in PDE4 B,but not PDE4 D,displayed similar effects to general PDE4 inhibition. In addition,rolipram reversed ethanol withdrawal-induced anxietyand depressive-like behaviors 1 d and 14 d,respectively,following withdrawal from ethanol drinking in the two-bottle choice in C57 mice or FH rats. Locomotor activity was not changed in either mice or rats treated with the PDE4 inhibitors. Levels of cAMP,p CREB in the brain were increased by rolipram.CONCLUSION The results provide solid evidence for the important role of PDE4 in ethanol consumptionand ethanol withdrawal-induced symptoms. Inhibitors of PDE4,in particular the PDE4 B isoform,can be a novel class of treatment for alcoholism.
文摘Great variability exists in the response to painful experimental stimuli, in the pain experienced between individuals with similar injuries, in the susceptibility to chronic pain, and in the response to analgesic treatments. Genetic factors account for a significant proportion of the variability, but have only recently been systematically studied. Comprehensive surveys of the sensitivity of inbred mouse strains demonstrate the remarkable heritability
基金supported by Nebraska Cancer and Smoking Disease Research Programs LB506and LB595 to CS BOCKMAN and DJ STAIRS
文摘OBJECTIVE Individuals vary in sensitivity to the behavioral effects of nicotine,resulting in differences in their vulnerability to addiction.The role of rearing environment in determining individual sensitivity to nicotine is unclear.The neuropharmacological mechanisms mediating the effect of rearing environment on the actions of nicotine are also understood.Thus,the contribution of rearing environment in determining the sensitivity to the locomotor effects of nicotine and regulating α4β2*-and α7-nicotinic acetylcholine(n ACh) receptor expressionwas determined in rats reared in isolated(IC) or enriched(EC) conditions.METHODS To measure locomotor activity,adolescent rats(postnatal day 21-51)were injected with saline(1 mL·kg^(-1)) or nicotine(0.3 mg·kg^(-1)) subcutaneously,then placed in chamberswhere ambulatory activity was monitored for 30-min by computer for 14 daily sessions.α4β2*-andα7-n ACh receptor expression in the mesolimbic dopamine pathway was determined by quantitative autoradiography of [125 I]-epibatidine and [125 I]-bungarotoxinbinding,respectively,in 16 μmol·L^(-1) coronal sections.Values for receptor expression in fmol are ±s of 8 brains and compared by two-tailed,unpaired t-test with P<0.05 considered significant.RESULTS EC-rats are similarly sensitive as IC-rats to the locomotor effects of nicotine.[125 I]-epibatidine binding in the ventral tegmental area of EC-rats was reduced(2.8±0.3 fmo L) compared to IC-rats(4.0±0.4 fmo L);there was no difference in the nucleus accumbens.There was no difference between EC-and IC-rats in α7-n ACh receptor expression in the mesolimbic dopamine pathway.CONCLUSION Rearing environment differentially regulates n ACh receptor subtypes in EC and IC rats.These data suggest regulation of n ACh receptors by environmental factors may be a mechanism for the protective effect of enrichment against altered sensitivity to nicotine in genetically vulnerable individuals.The characterization of these mechanisms will aid in development of novel pharmacological tools mimicking the protection afforded by environmental enrichment in nicotine-sensitive individuals.
文摘The central purpose of this paper is to explain how Darwin′s theory of evolution by natural selection can be used in understanding current human behaviour. First, Darwin′s logic is briefly described. Development is an important issue when applying evolutionary theory to human behaviour. The notion of innate developmental organization of psychological mechanisms is introduced. The possible social and political outcomes produced when different levels of innate developmental organization are paired with different beliefs about it are considered. The notion of psychological mechanisms as evolved adaptations is considered in some detail. Then I discuss different ways evolutionists think about how genes are involved in the development of adaptations. The paper concludes with a framework for considering how ancestral adaptations function in current environments and outlines some ways of studying them. In China and many other parts of the world people desire a more harmonious society. I hope that this paper will be of some small help in achieving this great task.
文摘Occupational Health Psychology(OHP)is an interdisciplinary field concerned with psychological factors in employee's health,safety,and well-being,closely related to Industrial/Organizational(I/O)Psychology. Specific areas of concern are accidents,injuries,illness,stress,violence,counterproductive work behavior,and work-family conflict. Based on his research,Dr. Paul E. Spector answered our questions on aspects of Occupational Health Psychology,Cross-cultural Psychology and research/statistical methods in I/O Psychology. His opinions or suggestions about future research in I/O Psychology are informative and inspiring.
