A quantifiable behavioral correlate of psychotogen and tranquilizer actions

A representative psychotogen, lysergic acid diethylamide (LSD-25), in doses small enough to be devoid of gross effects, increases response latency in rats to a tone indicating the availability of water reward; this effect is greatly reduced by prophylactic administration of a representative phenothiazine tranquilizer, chlorpromazine (CPZ), in doses that per se do not affect performance. The nature of the chlorpromazine action and its competition with lysergic acid diethylamide is revealed by the effects of chlorpromazine in larger doses.     

Preference for vibrational over translational energy in a gas-surface reaction

State-resolved gas-surface reactivity measurements revealed that vibrational excitation of nu3 (the antisymmetric C-H stretch) activates methane dissociation more efficiently than does translational energy. Methane molecules in the vibrational ground state require 45 kilojoules per mole (kJ/mol) of translational energy to attain the same reactivity enhancement provided by 36 kJ/mol of nu3 excitation. This result contradicts a key assumption underlying statistical theories of gas-surface reactivity and provides direct experimental evidence of the central role that vibrational energy can play in activating gas-surface reactions.     

CB1 cannabinoid receptors and on-demand defense against excitotoxicity

Abnormally high spiking activity can damage neurons. Signaling systems to protect neurons from the consequences of abnormal discharge activity have been postulated. We generated conditional mutant mice that lack expression of the cannabinoid receptor type 1 in principal forebrain neurons but not in adjacent inhibitory interneurons. In mutant mice,the excitotoxin kainic acid (KA) induced excessive seizures in vivo. The threshold to KA-induced neuronal excitation in vitro was severely reduced in hippocampal pyramidal neurons of mutants. KA administration rapidly raised hippocampal levels of anandamide and induced protective mechanisms in wild-type principal hippocampal neurons. These protective mechanisms could not be triggered in mutant mice. The endogenous cannabinoid system thus provides on-demand protection against acute excitotoxicity in central nervous system neurons.     

An identified neuron (CPR) evokes neuronal responses reflecting food arousal in Aplysia

Feeding behavior of Aplysia is associated with an arousal state characterized by a constellation of maintained behaviors and by a potentiation or depression of responses to specific stimuli. A neuron (the cerebral-pedal regulator or CPR) that has widespread actions on various systems connected with feeding has been identified. CPR excites neurons that modulate or drive (i) body posture, (ii) biting, and (iii) cardiovascular behaviors. CPR also inhibits neurons concerned with defensive responses. Food stimuli, which elicit food arousal in the animal, produce prolonged excitation of the CPR. The results suggest that the CPR may evoke a central motive state representing the neuronal correlate of feeding motivation.     

Lysergic acid diethylamide: dissociation of its behavioral and hyperthermic actions by DL-alpha-methyl-p-tyrosine

Rabbits treated with LSD 25 exhibit characteristic signs of hyper-excitability, increased peripheral sympathetic activity, and hyperthermia. When the rabbits received prior treatment with DL-(alpha)-methyl-p-tyrosine, the excitation and sympathetic actions of LSD 25 were abolished or attenuated, but the hyperthermia was unchanged from that of the controls. Concentrations of norepinephrine in brain stems of treated rabbits were greatly decreased. The excitation of central nervous system and sympathomimetic actions of LSD 25 in the rabbit are apparently mediated by norepinephrine, whereas the hyperthermic action functions. through a nonadrenergic mechanism.     

Holes in a Quantum Spin Liquid

Magnetic neutron scattering provides evidence for nucleation of antiferromagnetic droplets around impurities in a doped nickel oxide-based quantum magnet. The undoped parent compound contains a spin liquid with a cooperative singlet ground state and a gap in the magnetic excitation spectrum. Calcium doping creates excitations below the gap with an incommensurate structure factor. We show that weakly interacting antiferromagnetic droplets with a central phase shift of pi and a size controlled by the correlation length of the quantum liquid can account for the data. The experiment provides a quantitative impression of the magnetic polarization cloud associated with holes in a doped transition metal oxide.     

Unexpected adrenergic effects of chlorpromazine: eating elicited by injection into rat hypothalamus

Although chlorpromazine is believed to block adrenergic transmission, injection of this drug into the hypothalamus of satiated rats does not block norepinephrine-elicited eating, but instead mimics norepinephrine by eliciting eating. The amount of eating elicited by norepinephrine and by chlorpromazine is reliably correlated. These results suggest that endogenous norepinephrine mediates eating elicited by centrally injected chlorpromazine.     

Optical pumping and vibrational cooling of molecules

The methods producing cold molecules from cold atoms tend to leave molecular ensembles with substantial residual internal energy. For instance, cesium molecules initially formed via photoassociation of cold cesium atoms are in several vibrational levels nu of the electronic ground state. We applied a broadband femtosecond laser that redistributes the vibrational population in the ground state via a few electronic excitation/spontaneous emission cycles. The laser pulses are shaped to remove the excitation frequency band of the nu = 0 level, preventing re-excitation from that state. We observed a fast and efficient accumulation ( approximately 70% of the initially detected molecules) in the lowest vibrational level, nu = 0, of the singlet electronic state. The validity of this incoherent depopulation pumping method is very general and opens exciting prospects for laser cooling and manipulation of molecules.     

Chlorpromazine and its metabolites alter polymerization and gelation of actin

Hepatic hydroxylated metabolites of chlorpromazine (10(-5)M to 10(-4)M), a frequently used phenothiazine tranquilizer, produce solid gel formation with filamentous actin, but the less toxic chlorpromazine sulfoxide metabolite does not. At higher concentrations (5 x 10(-4)M) chlorpromazine inhibits actin polymerization. These dose-response relationships parallel the drug's hepatic toxicity in vivo and suggest that interactions between chloropromazine or chlorpromazine metabolites and actin could be an underlying mechanism of cell injury.     

Real-time observation of adsorbate atom motion above a metal surface

The dynamics of cesium atom motion above the copper(111) surface following electronic excitation with light was studied with femtosecond (10(-15) seconds) time resolution. Unusual changes in the surface electronic structure within 160 femtoseconds after excitation, observed by time-resolved two-photon photoemission spectroscopy, are attributed to atomic motion in a copper-cesium bond-breaking process. Describing the change in energy of the cesium antibonding state with a simple classical model provides information on the mechanical forces acting on cesium atoms that are "turned on" by photoexcitation. Within 160 femtoseconds, the copper-cesium bond extends by 0.35 angstrom from its equilibrium value.     

Femtosecond Dynamics of Excited-State Evolution in

Time-resolved absorption spectroscopy on the femtosecond time scale has been used to monitor the earliest events associated with excited-state relaxation in tris-(2,2'-bipyridine)ruthenium(II). The data reveal dynamics associated with the temporal evolution of the Franck-Condon state to the lowest energy excited state of this molecule. The process is essentially complete in approximately 300 femtoseconds after the initial excitation. This result is discussed with regard to reformulating long-held notions about excited-state relaxation, as well as its implication for the importance of non-equilibrium excited-state processes in understanding and designing molecular-based electron transfer, artificial photosynthetic, and photovoltaic assemblies in which compounds of this class are currently playing a key role.     

Ultrafast interfacial proton-coupled electron transfer

The coupling of electron and nuclear motions in ultrafast charge transfer at molecule-semiconductor interfaces is central to many phenomena, including catalysis, photocatalysis, and molecular electronics. By using femtosecond laser excitation, we transferred electrons from a rutile titanium dioxide (110) surface into a CH3OH overlayer state that is 2.3 +/- 0.2 electron volts above the Fermi level. The redistributed charge was stabilized within 30 femtoseconds by the inertial motion of substrate ions (polaron formation) and, more slowly, by adsorbate molecules (solvation). According to a pronounced deuterium isotope effect (CH3OD), this motion of heavy atoms transforms the reverse charge transfer from a purely electronic process (nonadiabatic) to a correlated response of electrons and protons.     

HPLC-MS法测定猪肉中地西泮等5种禁用药物的残留量

[目的]建立快速、准确、高灵敏度的测定猪肉中地西泮等5种禁用药物残留量的分析方法。[方法]采用高效液相色谱-串联质谱联用法(HPLC-MS),通过不同的离子模式进行猪肉中5种禁用药物残留量的测定,其中地西泮、丙酸睾酮、氯丙嗪采用正离子模式,玉米赤霉醇以及己烯雌酚采用负离子模式,并进行多反应检测(MRM)。[结果]试验显示,该方法的线性范围为:3~100 ng/m L,标准曲线线性良好,其回归方程及相关系数分别为地西泮:Y=27 200X-0.009 31,R=1.000 0;丙酸睾酮:Y=13 800X-0.000 147,R=1.000 0;氯丙嗪:Y=0.095 1X+0.025 7,R=0.999 9;玉米赤霉醇:Y=44 100X-0.006 58,R=1.000 0;己烯雌酚:Y=0.093 4X+0.018 8,R=0.998 9。回收率分别为:地西泮100.50%~111.30%;丙酸睾酮73.30%~84.20%;氯丙嗪70.30%~99.10%;玉米赤霉醇69.90%~75.30%;己烯雌酚84.70%~117.70%。最低检出限分别为:地西泮0.4μg/kg,丙酸睾酮0.6μg/kg,氯丙嗪0.3μg/kg,玉米赤霉醇0.5μg/kg,己烯雌酚0.8μg/kg。[结论]该方法操作简便、快速,是动物源性食品中地西泮等5种禁用药物残留的快速而准确的检测方法。     

Ischemic necrosis: prevention by stress

Complete interruption of the circulation, by means of a special clip, in a skin flap during 9 hours results in necrosis of the ischemic area. Prior treatment with various severe stressors (spinal-cord transection, prolonged restraint, quadriplegia due to transection of motor nerves, forced exercise, or cold baths), as well as systemic injection of epinephrine, norepinephrine, or chlorpromazine, offers virtually complete protection against this form of topical tissue injury.     

Compulsive sexual activity induced by p-chlorophenylalanine in normal and pinealectomized male rats

p-Chlorophenylalanine depletes brain serotonin and induces longlasting sexual excitation in male rats. The effect of p-chlorophenylalanine is potentiated by pargyline. Administration of 5-hydroxytryptophan to rats treated with p-chlorophenylalanine plus pargyline blocks the sexual excitation. p-Chlorophenylalanine also elicits sexual excitation in pinealectomized rats; this effect is not mediated by the lack of indole hormones in the pineal but may be the consequence of depletion of 5-hydroxytryptophan in the brain and the resulting imbalance between 5-hydroxytryptophan and catecholamine activity in the central nervous system.     

Genetic Self-Incompatibility in Oenothera subsect Euoenothera

Although it has been postulated that genetic self-incompatibility was involved in the origin of complex heterozygotes in Oenothera subsect Euoenothera, it has not been detected in any species of this well-studied group. It is now reported for populations of Oenothera grandiflora from west central Alabama, and should be sought in other populations of this species, which has been in cultivation for nearly two centuries.     

CNS and hypoderm regulatory elements of the Drosophila melanogaster dopa decarboxylase gene

Expression of the dopa decarboxylase gene (Ddc) is regulated in a tissue- and developmental stage-specific manner throughout the life cycle of the fruit fly, Drosophila melanogaster. Essential Ddc regulatory elements lie within 208 base pairs upstream from the RNA start point. Functional elements within this 5' flanking region were mapped by deletion analysis, which assayed expression in vivo after germline integration via P element vectors. One of the elements is essential for expression in both the larval and adult central nervous system, and at least two other elements are necessary for quantitatively normal expression in the hypoderm. Within each of the intervals that have regulatory effects are found sequence elements conserved between the Ddc genes of two distantly related species of flies. On the basis of this correlation, regulatory functions for these sequence elements can be postulated.     

Neuroleptic drug-induced dopamine receptor supersensitivity: antagonism by L-prolyl-L-leucyl-glycinamide

An animal model of tardive dyskinesia was used to evaluate the potential antidyskinetic properties of the neuropeptide L-prolyl-L-leucyl-glycinamide (PLG). In rats, PLG administered concurrently with the neuroleptic drug haloperidol or chlorpromazine antagonized the enhancement of specific [3H]spiroperidol binding in the striatum that is associated with long-term neuroleptic treatment. The results are discussed in relation to a possible functional coupling of the putative PLG receptor with neuroleptic-dopamine receptor complex and clinical implications for tardive dyskinesia.     

科研项目资金管理刍议——兼议《意见》的指导作用

当前我国科研人员窘迫的收入情况与日益增加的中央财政科研投入形成鲜明的反差。国务院颁发的《关于改进加强中央财政科研项目和资金管理的若干意见》,对这种科研分配的不合理现状进行了针对性改进。该文结合当前项目的申请、执行、预算、绩效等争议热点,对该《意见》对科研管理工作的实质性指导意义进行了简要阐述。     

Loss of M2 muscarine receptors in the cerebral cortex in Alzheimer's disease and experimental cholinergic denervation

Cerebral cortex samples from patients with Alzheimer's disease and from rats after experimental cholinergic denervation of the cerebral cortex exhibited reductions in the presynaptic marker choline acetyltransferase activity and in the number of M2 muscarine receptors, with no change in the number of M1 receptors. These results are in keeping with evidence that M2 receptors function in cholinergic nerve terminals to regulate the release of acetylcholine, whereas M1 receptors are located on postsynaptic cells and facilitate cellular excitation. New M1-selective agonists and M2-selective antagonists directed at post- or presynaptic sites deserve consideration as potential agents for the treatment of the disease.