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Biomedical subjects

N Kosaka

Publications and source records attributed to N Kosaka.

At least 73 records · Page 4Linked to original sources
PubMed1983

[Determination of mental dependence liability of drugs using small animals. 3. Selective drinking behavior of mice caused by dependence-liable drugs].

Using mice, drug solution-directed drinking behavior was investigated in the choice test between drug solution and tap water following various regimes of pretreatment. In the preliminary experiments, the concentration of the drug solution for the pretreatment and choice test and also the dose of injection was determined for each drug, depending on the amount of the drug to produce its CNS action without any undesirable toxic effect. The duration of pretreatment and the succeeding choice test was also settled as 6 days. Animals forcedly given morphine or cocaine as the drinking solution during pretreatment showed elevated preference for drug solution in the choice test. High grade preference was demonstrated for cocaine and amphetamine solution after pretreatment with injections of the drugs. Combined pretreatment potentiated the effect of these drugs. With barbital or ethanol, no appreciable reinforcing effect was found under the present experimental conditions. Thus, in addition to the experience with the drug solution, the injection of the drug facilitated the development of preference for the drug and demonstrates the positive reinforcing properties of the drugs which possess high grade psychic dependence liability. The validity of mice for the purpose of screening psychic dependence liable drugs and the restrictions on its application are discussed.

Animals↗
PubMed1982

[Studies on the physical dependence liability to guanabenz].

The physical dependence liability of guanabenz, a hypotensive agent with central noradrenergic alpha 2-agonistic activity, was investigated. 1) Guanabenz showed a potent analgesic effect nearly equipotent to morphine by the modified Haffner's method, and repeated p.o. treatment resulted in the development of tolerance to the effect. 2) In the combined treatment of guanabenz with morphine or hexobarbital, it potentiated morphine analgesia and prolonged hexobarbital hypnosis in a dose dependent manner. 3) The natural withdrawal signs appearing in morphine or barbital dependent mice was suppressed by guanabenz; however, the effect was accompanied by a marked loss of body weight and weakness of the animals, and especially the dose required for the suppression of barbital withdrawal signs was extremely high and was even lethal in some cases. A substitution test in barbital dependent mice showed that guanabenz could not substitute for barbital. In the primary dependence test after 30 days oral treatment with guanabenz, no appreciable withdrawal signs were observed after discontinuation of the administration. Thus, from the results obtained in the present experiments, it is revealed that guanabenz possesses no physical dependence liability of the morphine or barbital type.

Analgesics↗
PubMed1982

[Determination of the development of psychotic dependence to drugs in small animals. 4. Selective drinking of barbital and ethanol solutions by mice].

Using mice, preference for barbital or ethanol solution was examined in choice test between drug solution and tap water after pretreatment with the drugs for 6, 15 or 30 days under different conditions, a) forcedly given the drug solution as drinking liquid. b) ip injected the drug twice daily, c) combined treatment, forced drinking plus ip injection. Pretreatment with barbital induced aversion to the drug solution regardless the conditions of pretreatments mainly because the unpalatability of the drug solution and also the unpleasant effect of injected drug. In ethanol pretreated animals, pre-exposure to ethanol solution decreased the preference ratio for the drug solution n choice test but accustomed to the taste in parallel with the duration of the pretreatment. After treatment with injection, on the other hand, animals acquired preference for ethanol solution indicating the reinforcing effect of the injected drug. Six days pretreatment with the drugs developed tolerance to their suppressive effect and in barbital treated animals physical dependence was also developed. However, the degree of preference or drug solution was not parallel to the intensity of tolerance or physical dependence. Characteristics of the test drugs as reinforcer of drinking behavior was easily determined by this method and its validity for the screening of the drugs of psychic dependence liability was suggested.

Animals↗
PubMed1981

[Determination of the development of psychotic dependence to drugs in small animals. 2. Selective drinking of morphine and cocaine solutions and its reinforcement in mice].

To develop a screening method for psychic dependence liability of the drugs, morphine- and cocaine-directed drinking behavior was studied in mice. Using automatic drinkometer the intake of drug solution from the paired sucking tube connected to tap water and/or drug solution was estimated. The drinking pattern showed a diurnal rhythm and large portion of the total intake was done during dark period. When the animals were forcedly given drugs as drinking solution total intake and the gain of body weight was suppressed in proportion to the concentration of the drugs. In the choice test between tap water and drug solution, mice can distinguish the concentration of drug solution and avoid it in high concentrations. Animals experienced drug solution before the choice test showed a tendency to intake more drug solution than the untreated control animals depending on the length of pretreatment. Pretreatment of the animals with twice daily injections of the drugs failed to develop high grade of preference to drug solution in the succeeding choice test. Thus, the positive reinforcing properties of morphine and cocaine was demonstrated in mice and the validity of this animal species for the screening of the drugs of psychic dependence was suggested.

Animals↗
PubMedDate not supplied

Timing of cycloheximide administration and inhibition of the development of analgesic tolerance to morphine.

A single injection of cycloheximide (10 mg/kg, i.p.) partially prevented the development of analgesic tolerance to morphine (10 mg/kg, i.p. daily for 5 days). The inhibitory effect of cycloheximide was strictly dependent on the time of its administration, and only effective when it was administered 2 hrs before or 1 hr after morphine injection. Daily repeated treatment with cycloheximide 2 hrs before and/or 1 hr after morphine also prevented the tolerance development. However, the pre or post treatment with cycloheximide differed in the duration of the effect, and the discrepancies between two treatments suggest the importance of timing of the administration of inhibitor in the underlying mechanisms.

Analgesia↗
PubMedDate not supplied

Effect of cervical spinal cord stimulation (cSCS) on cerebral glucose metabolism and blood flow in a vegetative patient assessed by positron emission tomography (PET) and single photon emission computed tomography (SPECT).

This paper presents, for the first time, assessments of cerebral glucose metabolism and cerebral blood flow before and after cervical spinal cord stimulation (cSCS) in a vegetative patient. Regional cerebral metabolic rates for glucose (rCMRglc) were measured with positron emission tomography and 18F-fluoro-2-deoxy-D-glucose. Regional cerebral blood flow (rCBF) was determined with single photon emission computed tomography and N-isopropyl p-123I-iodoamphetamine. Global CMRglc in the patient was less than one-third of that in normal control subjects. An increase in rCMRglc after one week of cSCS was observed in the cerebral cortex, predominantly on the right side, where the baseline level of rCMRglc before cSCS was more severely depressed. The pattern of increase in rCBF was almost the same as that in rCMRglc. The results suggest that cSCS activates glucose metabolism and that this is followed by an increase in cerebral blood flow.

Amphetamines↗
PubMedDate not supplied

A new method for brain functional study using Tc-99m HMPAO SPECT.

The distribution of 99mTc-HMPAO in brain is in proportion to regional cerebral blood flow (rCBF) and can be interpreted as functional mapping. To evaluate local changes in CBF during neuropsychological testing, we developed a new subtraction method using HMPAO and SPECT. With patients resting, 15 mCi of HMPAO was injected and the first acquisition was performed, lasting a total of 10 minutes. Soon after the end of the first scan, patients were requested to undergo Buschke's memory test or to repeat words or numbers (repetition test). During the task, an additional 15 mCi of HMPAO was injected using the same position as in the first scan, and a second acquisition was started. A functional image was made by subtracting the image in the first scan from that in the second. In two patients with transient global amnesia and two normal controls, Buschke's memory test was performed in combination with SPECT. A Relative increase in activity was seen in the thalamus, subthalamic area, hippocampus, and some cortical areas, apparently reflecting local functional change induced by the memory task. In two patients with moderate Alzheimer's disease with severe memory loss, no increase was detected in these areas. In one patient with aphasia, the repetition test with SPECT was correlated with the WADA test and dichotic listening test, and good agreement was obtained. In conclusion, our new SPECT technique is useful in detecting alterations in rCBF during mental activity and can be applied to neurophysiological studies.

Alzheimer Disease↗