Negative and positive intracranial reinforcement tresholds: Effects of morphine

Negative (aversive) and positive (self-stimulation) intracranial reinforcement thresholds were determined in rats using a double staircase psychophysical procedure. Morphine raised aversive thresholds at all doses tested, while the drug lowered positive reinforcement thresholds at low or moderate doses. The results suggest the possible involvement of central motivational systems in the mediation of morphine-induced analgesia, the narcotic high, and narcotic addiction.This paper is based on a dissertation submitted by the first author in partial fulfillment of requirements for the Ph. D. degree in the Department of Psychology, Boston University, and was supported in part by grants MH 12568 and DA 00257 from the National Institute of Mental Health.     

Dynamic aspects on acute tolerance to hexobarbital evaluated with an anesthesia threshold

Induction of acute tolerance was studied with hexobarbital in male rats. A threshold technique utilizing an EEG-criterion consisting of a burst suppression of 1 second or more (the SS) was used both to induce and maintain anesthesia. Hexobarbital was infused with an optimal dose rate of 15 mg/kg/min. The infusion was stopped at the criterion and restarted when no SS had been seen for 1 min. The doses of hexobarbital needed to maintain anesthesia were fairly constant around 3.5 mg/kg/min up to durations of 120 min which indicates that redistribution of hexobarbital is of minor importance in the present experiments. After different predetermined times of this fairly stable anesthesia, the rats were sacrificed, and concentrations in the cortex of the brain were determined with a HPLC-method. Maximal induction of acute tolerance was seen as a 45 percent increase in cortex concentration after 60 min of anesthesia, but already after 10 min a slight acute tolerance was recorded.     

Sensory irritation caused by various industrial airborne chemicals

A short inhalation experiment was performed on mice using 22 industrial airborne irritants. The parameter chosen as an index of sensory irritation was the reflex decrease in respiratory rate. For each compound, systematic determination of the concentration associated with a 50% decrease in the respiratory rate (RD5o) permitted, on the basis of the same end point, a comparison of their relative potencies.The possibility of using the obtained data as initial guidelines to establish acceptable Threshold Limit Values (TLVs) in the workplace was examined.     

Morphology and electrophysiology of ventral mesencephalon nerve cell cultures

Electrophysiological changes occurring during the development of a kindled focus in the CA₁ region of the rat hippocampus were studied in vivo. The most conspicuous changes of the field potentials (EPs) recorded from the stratum radiatum to stimulation of the Schaffer collaterals were the following: (1) a progressive decrease of the slope of the decaying phase of the EPs which was significantly different (P < 0.02) from controls from sessions 8–12 onwards; (2) in the EPs recorded from the stratum pyramidale/oriens a population spike emerged from sessions 7–10 onwards; the ratio amplitude of the population spike/slope of the local EP increased progressively from session 8 onwards until a saturation level was reached; and (3) a progressive attenuation of paired-pulse depression; this decreased linearly with kindling session from session 1 up to session 11 (r = 0.97, P < 0.01) and thereafter stabilized. These results are interpreted as due to a progressive imbalance between excitatory and inhibitory processes resulting in a decrease of inhibitory control in CA₁ accompanied by a decrease in threshold of pyramidal neurons.     

Temporary threshold shift of vibratory sensation induced by a vibrating handle and its gripping force

•Objective This study examines the effect of the force with which a vibrating handle is gripped on the temporary threshold shift of vibratory sensation (TTS_v) induced by hand-arm vibration. •Methods Six healthy subjects gripped a handle vibrating with a 1/3 octaveband vibration, with a central frequency of 200 Hz and an intensity of 39.2 m/s². Exposure was for 1 min and 10 min, respectively. Gripping forces for the 1-min exposure were 5 N, 10 N, 40 N and 80 N, respectively, with 0 N push-pull force. Gripping forces for the 10-min exposure were the same as for the 1-min exposure, but omitting 80 N. The vibratory sensation threshold at 125 Hz was measured before and after exposure of an exposed fingertip to vibration. The differences measured determine TTS_v,t at timet. TTS_v,t determines TTS_v,0, that is, the temporary threshold shift of vibratory sensation immediately after exposure to vibration according to the estimate made on the basis of the preceding study. The same experimental conditions were repeated 3 times on different days in a soundproof and thermoregulated room. •Results Our findings show that TTS_v increases significantly with increasing gripping force. We also determined the quantitative relationships between TTS_v,0 and gripping force as described by the equation wherek _f andc _f are constants andF is gripping force. •Conclusion This study revealed the importance of ergonomic design in reducing the force with which a vibrating handle is gripped to prevent an adverse effect of local vibration. The equation devised may help in the quantitative assessment of the effect of reduced gripping force.     

The antagonism between reserpine and some antiparkinson drugs in electroseizure

Summary The effects of amphetamine, metamphetamine, propylhexedrine, biperiden and atropine were studied in experiments on electroseizure threshold in rats. In high doses these drugs lowered the threshold of electroseizures and antagonized the threshold lowering produced by reserpine, with the exception of atropine, which enhanced the action of reserpine. Low doses of the drugs and combinations of low doses of metamphetamine, propylhexedrine and biperiden did not influence electroseizure threshold, but inhibited the action of reserpine. The effect of phenytoin on the threshold lowered by reserpine was enhanced by low doses of metamphetamine, propylhexedrine and biperiden. Tetrabenazine caused threshold lowering which was antagonized by metamphetamine, propylhexedrine, biperiden and atropine. Pretreatment with -methyl-p-tyrosine, but not with diethyldithiocarbaminate abolished the effect of high doses of metamphetamine or propylhexedrine on the electroseizure threshold. Inhibition of the formation of DOPA or noradrenaline did not influence the action of reserpine or the antagonism between reserpine and the drugs of the amphetamine group. After a repeated injection of metamphetamine tachyphylaxis developed.Supported by a grant of the Deutsche Forschungsgemeinschaft.     

Magnetic stimulation in Alzheimer’s disease

Alzheimer’s disease (AD) is a common cause of dementia in which some clinical motor abnormalities have been described. We used transcranial magnetic stimulation in order to test the hypothesis that the change in the motor cortex might cause modifications in motor excitability. Fourteen mildly to moderately affected AD patients were compared with 11 controls matched for age, height and sex. The motor evoked potential threshold value for the relaxed abductor digiti minimi was lower in the AD patients than in the control group for both left and right hemispheres (P < 0.05). No statistically significant difference was found comparing the left and the right hemispheres thresholds in each population. The mean interside threshold differences were small and not significantly different between patients and controls. The spinal motor neuron excitability, as evaluated by F/M and H/M waves amplitude ratios, showed no difference between the groups, reinforcing the motor cortex increased excitability hypothesis to explain this difference. Degeneration of inhibitory gabaergic terminals might be the basis for the increased cortical excitability in the motor cortex of the Alzheimer patients; postsynaptic changes in the GABA_A receptors might also affect inhibitory gabaergic transmission. The increased excitability found by transcranial magnetic stimulation in the motor cortex is important for understanding the emergence of seizures and myoclonus in this disease. Received: 9 August 1996 Received in revised form: 14 February 1997 Accecpted: 20 February 1997     

Trichloro-compounds in the urine of humans exposed to methyl chloroform at sub-threshold levels

Summary Survey was carried out in 4 intaglio printing factories where methyl chloroform, the sole organic solvent in the entire process, was employed to remove excess ink. The medical interview and clinico-laboratory examinations revealed no dose-consistent adverse effects among the four groups of workers who had been exposed at the average concentrations of 4, 25, 28 and 53 ppm, respectively. Linear relationship was observed between environmental vapour concentrations and total trichloro-compounds levels in the urine of workers exposed. Increased levels of urinary metabolites towards the week-end, together with the biological half-life of 8.7 hrs as measured from the decrease in the urinary metabolites, suggested the storage of methyl chloroform in the body after repeated exposures. Perusal of previous reports as well as present results regarding toxic potency of methyl chloroform supports, with emphasis of possible accumulation, the German threshold of 200 ppm as a tentative value of choice for the time being.A part of this work was presented at the 46th Annual Meeting of the Japanese Association of Industrial Health, Osaka, April 6–8, 1973.     

Estimating chromatic contrast thresholds from the transient visual evoked potential

Chromatic contrast thresholds may be estimated from transient VEPs by measuring the peak-to-peak amplitude at a range of stimulus levels followed by extrapolation to zero amplitude. However, there have been reports of failure of this technique when applied to the transient chromatic VEP due to variability of amplitude, difficulties with component identification and poor correlation of amplitude with stimulus level. The aim of our study was to compare methods of transient VEP chromatic contrast threshold estimation in terms of success rate and comparison with psychophysical threshold. We found each of the methods we investigated to have a high success rate, and in most cases VEP and psychophysical thresholds did not differ significantly.     

氯喹在体外对疟色素形成的条件性抑制

目的 研究在体外系统中氯喹对疟原虫疟色素形成抑制作用的特点。 方法 利用光镜和分光光度法观察和检测不同浓度乙酸钠溶液（0.5、1、1.5和2 mol/L）在不同pH值（pH 4.0、4.2、4.4、4.6、4.8和5.0）条件下,氯喹对疟色素基质形态及其生成量的影响,观察疟色素形成基质的形态变化规律。同时,用X-射线衍射分析不同pH条件下氯喹对色素晶体的结晶度及晶体大小的影响。 结果 氯喹抑制疟色素形成的临界pH值随乙酸钠浓度的升高而升高,从0.5 mol/L乙酸钠时的pH 4.2到2 mol/L时的pH 4.8。X-射线衍射分析表明,环境pH值由4.4提高到4.8,疟色素晶体的结晶度和晶体大小也分别从6.93%和357 ?魡下降到6.32%和264 ?魡。当pH值升高到5.0时,β-hematin晶体不再形成。氯喹可降低相同pH条件下β-hematin晶体的结晶度和晶体大小。形态学观察结果与之一致。 结论 体外实验表明,氯喹仅在疟色素形成处于或大于临界pH时,才表现出抑制疟色素形成的作用。