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H Kaneto

Publications and source records attributed to H Kaneto.

At least 163 records · Page 9Linked to original sources
PubMed1984

[Acquisition of a lever press behavior by mice in a water reinforcement situation].

An operant chamber for mice, consisting of two adjacent compartments of W 130 X L 120 X H 150 mm, with a liquid dispenser which is operated by lever press was prepared. Using the apparatus, the applicability of mice for the study of learning of lever press behavior in a water reinforcement situation was investigated. Animals were deprived of water in the home cage and water was only supplied in the operant chamber by the lever press. A session of 15 min training was performed daily. By continuous reinforcement schedule, animals learned the lever pressing by 3 sessions. With these trained animals which attained more than 150 responses further experiments with a fixed ratio (FR) schedule was made, from FR 1 to FR 20. The best increase in responses was observed when the FR was regularly and gradually stepped up from 1 to 20 by every 5 sessions. Scopolamine, 1 mg/kg ip, significantly suppressed the lever press at FR 1 sessions, and the latency time until the first lever press was also prolonged significantly in these sessions. Thus, the applicability of mice for the study of learning of lever press behavior and the experimental schedules were established.

Animals↗
PubMed1983

Changes of lipid peroxidation in mouse brain crude synaptosomal preparations in relation to the development and disappearance of tolerance to ethanol.

A single dose of ethanol induced a bimodal increase of Fe++- and ascorbic acid-stimulated lipid peroxidation in mouse brain crude synaptosomal preparations. This effect of ethanol was lost in preparations from ethanol tolerant animals and reappeared when the animals recovered from tolerance after withdrawal from ethanol treatments. The parallel changes in lipid peroxidation of brain crude synaptosomal preparations with the development and disappearance of tolerance to ethanol imply that the effect of ethanol on brain lipid may be directly associated with its mechanism in the CNS.

Animals↗
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

Further studies on the determinant role of brain level of pentobarbital for the development of acute hypnotic tolerance.

Controlling the brain level of pentobarbital and the duration of hypnosis at the initial treatment in relation to development of acute hypnotic tolerance was studied. Simultaneous treatment of bemegride or TRH with pentobarbital attenuated the hypnotic effect of pentobarbital in a dose dependent manner, but neither the brain level of pentobarbital nor the development of tolerance was modified by this treatment. The effect of TRH was further demonstrated in rats by concomitant intracarotidal infusion with pentobarbital maintaining the brain concentration of pentobarbital and also the duration of exposure of the brain to pentobarbital under a constant condition. On the other hand, THC significantly prolonged the hypnosis induced by pentobarbital but did not potentiate the effect of pentobarbital to develop acute tolerance. Thus, the brain level of pentobarbital at the initial treatment is the primary determinant for the development of acute tolerance and the duration of hypnosis is not the essential factor in this mechanism.

Animals↗
PubMed1981

[Studies on the barbital-type physical dependence liability of mequitazine in mice and rats (author's transl)].

Mequitazine is a new phenothiazine derivative with potent antihistaminic activity developed by Pharmuka, Co. Ltd., in France. Although the action of this drug on central nervous system is reported to be very weak in the dose range used as antihistaminics, the CNS action cannot be neglected when the huge amount is applied. In order to predict the safety use of this drug in clinical therapy the ability to develop barbital-type physical dependence was investigated. In conclusion, a single dose suppression test and substitution test in barbital dependent mice, and also the primary dependence liability test after repeated administration of the drug in rats revealed that Mequitazine has no physical dependence liability even in the toxic dose.

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↗
PubMed1980

Brain level of pentobarbital is the primary determinant for the development of hypnotic of hypnotic tolerance in mice.

Controlling the duration of hypnotic effect of pentobarbital by simultaneously administered bemegride, the relationship between the duration of hypnosis and the degree of developed tolerance after acute or chronic treatment was investigated in mice. Bemegride attenuated the hypnotic effect of pentobarbital, but neither the brain level of pentobarbital nor the development of tolerance was modified by bemegride, indicating that the brain level of pentobarbital is the primary determinant for the production of tolerance and full duration of hypnosis is not essential in this mechanism.

Animals↗
PubMed1980

[Tolerance to and dependence on opioids in isolated longitudinal muscle of guinea pig ileum. Validity of the muscle preparation as a receptor model for opioids (author's transl)].

Contractions evoked by electrical stimulation of isolated longitudinal muscle preparations of guinea pig ileum were inhibited by the addition of opioids in the order of morphine = methionine enkephalin greater than pentazocine pethidine. Incubation of the preparation in the medium containing opioids at 4 degrees C for 22 hr resulted in a tolerance to the inhibitory effect in morphine and pethidine but in the case of pentazocine and met-enkephalin tolerance did not develop under the conditions employed. The same treatment with morphine, pethidine and pentazocine resulted in the development of dependence as demonstrated by naloxone provoked contracture or increase in the height of contraction. Opiate and enkephalin receptors are known to be unevenly distributed in the ileum and a significant difference was also observed in the distribution patterns of both receptors. Distribution of the receptors did not parallel the effect of opioids, thereby indicating a multiplicity in receptors. However, under the conditions employed in the present experiments, our results reflect the in vivo effects of opioids, such as analgesic effect or tolerance and dependence liability, and the validity of this preparation for the evaluation of opioids was confirmed.

Animals↗
PubMed1979

Radioimmunoassay of methionine enkephalin and interference by brain factor of immunoreactivity and opiate receptor binding activity.

We developed a radioimmunoassay of methionine-enkephalin (met-enk) which was found to be highly specific to the peptide and 1 pmol was the detection limit. Interference by the following peptides was practically negligible; leucine-enkephalin, LAP- or CNBr-treated met-end, alpha- and beta-endorphins. Morphine and its congeners were totally inert. Measurement of met-enk in rat brain P2 fraction revealed besides met-enk, the presence of the factor which cross-reacted with the antiserum and also appeared to bind with the brain opiate receptor. Though the nature of the factor has not yet been characterized, it is suggested that for qualitative assessment of the tissue level of met-enk, a method to selectively inactivate either the peptide or the factor should be developed first.

Animals↗
PubMed1975

Drug metabolizing function of isolated perfused liver.

How closely the isolated liver of the rat would simulate the in vivo function of the organ in terms of the metabolic pattern of the compounds such as bromosulphophthalein, p-nitrophenol, hexobarbital, and indocyanine green was investigated. In order to produce tissue with the stimulated function, the animal was pretreated with phenobarbital and, for the reverse purpose, with ethionine. Some of the indices of the function employed herein, such as the appearance pattern of the compound, the rate of biochemical transformation or the biliary excretion, showed that the perfused liver would generally well reflect the in vivo situation. The method with isolated and perfused liver could exclude the participation of other organs and also the influence of the factors unavoidable in an in vivo experiment. Thus, it is suggested that the isolated perfused liver is useful for studying directly the functional level of the organ as drug metabolizing tissue.

Animals↗
PubMed1975

Protein synthesis in mouse brain during development of acute morphine tolerance.

In order to observe the effects of morphine on protein metabolism in mouse brain, experimental procedures were carried out over a 7 hr period of infusion. When the analgesia reached a peak, namely around 2 hr after the start of infusion, the in vivo incorporation of radioactive leucine into protein estimated by the dual label technique was uniformally depressed in all the examined subcellular fractions of both brain and liver. After tolerance developed, however, the incorporation of leucine increased to a much higher level than the control in brain subcellular fractions and the increase was masked by naloxone. In contrast, the incorporation into a TCA soluble fraction of the brain S2, separated by Gray and Whittaker's method, was more than doubled even after 4 hr infusion. While the in vitro incorporation rate of the mitochondrial fraction significantly fluctuated during development of tolerance with naloxone that of the synaptosomal fraction did not fluctuate. The observed coincidence in the time course of development of tolerance and changes in the brain protein synthesis indicates a possible relationship between the phenomena, though the causal nature of the relationship could not be elucidated.

Animals↗