Psychoactive drug effect on socio-environmental deprivation in rats.
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Biomedical subjects
Publications and source records attributed to L Valzelli.
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A considerable amount of evidence indicates that the brain tryptophan level depends on circulating tryptophan. Changes of tryptophan concentration have also been described to modify the activity of benzodiazepines and tricyclic antidepressants. In the present study, a series of psychoactive drugs have been preliminarily screened for their activity on brain and plasma tryptophan levels. The results obtained suggest that tryptophan may be involved to varying extents in the activity of different psychoactive compounds.
Piracetam has bee administered to young and old mice to investigate whether the age may differently modulate the activity of this centrally acting drug. After piracetam administration, old mice showed a notably greater increase of their brain tryptophan than young animals. Furthermore, piracetam significantly improves the learning capacity of young mice, but the drug is remarkably more active in improving the performance by old mice. These facts may then suggest that this compound is especially effective in restoring the neurobiological setting of the aging brain.
Circadian variations in whole brain tryptophan level and food intake were investigated in both normally grouped and isolated male Albino-Swiss mice, maintained on a 12:12 light-dark regimen (lights on 08.00--20.00). A significant diurnal rhythm in brain tryptophan level was evidenced only by grouped animals, in contrast to the relatively sustained and significantly lower tryptophan level found to exist in isolated mice. Significant, daily rhythms in food intake, for both isolated and grouped mice were found to exist, that were highly correlated in phase. Isolated mice, however, consistently demonstrated an increased food consumption throughout the 24-hour period. These results suggest that a possible alteration in tryptophan metabolism exists in isolated mice, as tryptophan, an essential amino acid, is obtained by mammals only through their diet.
The effect of p-chlorophenylalanine (PCPA) has been studied on the acquisition of avoidance learning and on brain concentrations of 5-hydroxytryptamine, 5-hydroxyindoleacetic acid and tryptophan of differentially housed male mice of Albino Swiss and DBA strains. The results obtained do not support the hypothesis that learning ability varies inversely with the concentration of brain 5-hydroxytryptamine. PCPA can appear as influencing learning ability of different strains of mice differentially housed, depending more on the emotional baseline of the animals than on brain 5-hydroxytryptamine modification.
In the framework of aggressive behavior a great amount of studies deal with altered brain monoamine levels or turnover. The involvement of brain serotonergic mechanisms in aggression has been demonstrated in the majority of the studies. In the present work, the biochemical and behavioral changes induced by prolonged socioenvironmental isolation in seven strains of mice were studied. Brain serotonin turnover varies significantly only in those strains which react to isolation with a constant degree of aggressiveness and there appears to exist an inverse correlation between these two parameters. Nevertheless a certain degree of aggression may develop even in the absence of alterations of brain serotonin turnover. Still the intensity of serotonin turnover decrease seems to represent a good indicator of the magnitude of the aggressive reaction.
Numerous studies have indicated that sulpiride exerts a positive effect upon several psychosomatic symptoms. This effect is generally believed to depend on the thymoanaleptic activity of the molecule. Since headache can often represent the warning symptom of a masked depression, in the present study sulpiride has been administered to patients suffering from nonorganic headache syndromes. The results obtained confirm the efficacy of sulpiride in relieving headache and other psychosomatic discomforts.
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Mice subjected to prolonged socioenvironmental deprivation gradually develop hyperirritability and hyperreactivity to physical stimuli. This heightened neuroexcitability may or may not debouch into aggressiveness according to strain and sex of the animals, and it is accompanied by a reduced sensitivity to CNS depressants. Socioenvironmental deprivation or isolation is shown to decrease the sensitivity either to pentobarbital or to ethanol potentiation of pentobarbital sleeping time in male mice from two different strains.
Isolation has been widely described to induce a strong aggressive behaviour in many animal species and especially in rodents. A deeper analysis of this altered behaviour induced by isolation, allows for the identification of several other changes involving numerous peripheral, behavioural and neurochemical functions. As a consequence of the manifold aspects involved in this experimental situation, the definition "isolation syndrome" seems to be much more adequate than the simplest definition of "aggressiveness by isolation". On this framework, some similarities with psychoneurosis in men are also suggested.
The annual and daily variations of brain serotonin and 5-hydroxyindolacetic acid have been studied over a 6-year period in normally grouped and isolated mice. The results obtained indicate that differences exist between normally grouped and isolated animals, especially when referred to the annual changes to which brain serotonin and 5-hydroxyindolacetic acid undergo. The results suggest that the outcome of the experiments on neurochemistry, neuropharmacology and behavior can change according to the month of the year and they can further be modified by differential housing of mice.
Prolonged isolation in mice is known to induce several behavioral changes, among which impairment of learning was also reported. On the other hand, alcohol is known to have either stimulant or depressant effects on behavior. Further, alcohol effect is also known to depend on strain-linked characteristics and on emotional ground of animals. Since prolonged isolation may differently change the emotional setting of mice, according to the strain, the behavioral effects of alcohol on avoidance learning, have been studied in two strains of male mice differentially housed. Evidences were obtained that ethanol can either improve or worsen learning performances according to the strain and the housing conditions adopted.
Several so-called 'non-specific' or 'non-drug' factors are known to interfere with the response to psychotropic drug administration. Animal emotionality has been reported to change the outcome of psychoactive drug administration, so that the response to a stimulant or depressant drug may considerably change according to the baseline state of activity of the central nervous system. Prolonged socio-encironmental deprivation or isolation has been shown to produce in rats three different types of abnormal behaviour which have been tentatively defined as 'friendly', 'indifferent' and 'muricide'. Such unusual changes in rat behaviour are assumed to reflect a series of different emotional changes. The present experiments show that psychoactive drugs can exert a different effect in relation to the different kinds of animal behaviour used in the experiments. The investigation of the properties of psychoactive compounds, as performed in experimental animals showing behavioural alterations, is then suggested as being more fruitful in providing much information closer to the clinical results than that achieved with the experiments performed in normal laboratory animals.
Lesion of the midbrain ventral raphe nucleus greatly improves the avoidance-learning efficiency of normal and isolated-aggressive Albino Swiss mice. Since the lesion of this brain area selectivity lowers the forebrain concentration of 5-hydroxytryptamine (5-HT), implications of the role of brain 5-HT in avoidance-learning acquisition are discussed.
The effects of long-term isolation of young adult male rats on the analgesic effects of morphine were investigated. Isolated rats developed altered patterns of behavior, including muricidal behavior in some animals. Analgesic activity of morphine was assessed with both the tail compression and the hot plate methods. The results indicate that chronically isolated rats, whether developing muricidal behavior or not, show no alteration in either pain thresholds or in their response to morphine-induced analgesia.
Although the effects of differential housing, particularly isolation, on the action of several classes of pharmacological agents have been studied, little attention has been given to this factor in regard to narcotics. The present study involves the effects of long-term social isolation on dependence to morphine produced by pellet implants in rats. When abstinence was precipitated with naloxone, isolated rats demonstrated less jumping and less diarrhea then grouped rats. No differences were found in other signs. In addition, the differences were seen both in isolates developing muricidal behavior and those not developing this behavioral pattern.