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Biomedical subjects

G Singer

Publications and source records attributed to G Singer.

At least 37 records · Page 2Linked to original sources

The action of corticosterone on schedule-induced wheelrunning.

Previous studies have shown that schedule-induced wheelrunning is dependent on an intact pituitary-adrenal axis, and thus the presence of circulating corticosterone. In the present study, the mechanism of action of corticosterone on schedule-induced wheelrunning was explored in two ways. In the first series of studies, the effect of different levels of corticosterone on schedule-induced wheelrunning in adrenalectomized rats was investigated; the results of this study show a dose-response relationship between levels of corticosterone and schedule-induced wheelrunning. In the second study, the glucocorticoid receptor subtype involved was determined by examining the effect of dexamethasone, a synthetic glucocorticoid, on schedule-induced wheelrunning in adrenalectomized rats. A low dose of dexamethasone effectively reversed the suppressant effect of adrenalectomy, suggesting that the behavioural action of glucocorticoids is mediated through classical (Type II) glucocorticoid receptors, and not through Type I, corticosterone-preferring receptors.

Adrenalectomy

The role of adrenal corticosterone in schedule-induced wheel running.

In 3 experiments, the role of adrenal corticosterone in schedule-induced wheel running was investigated. Data from the first experiment showed that bilateral adrenalectomy significantly suppressed schedule-induced wheel running, but did not influence non-scheduled wheel running. Results from a second experiment, where bilateral adrenalectomy with and without replacement of corticosterone was used, showed that the suppressant effect of adrenalectomy on schedule-induced wheel running was completely reversed by replacement of corticosterone. In Experiment 3, plasma corticosterone levels of all experimental rats were determined at the completion of the last test session. The results showed that a circulating level of corticosterone was necessary for the occurrence of schedule-induced wheel running. These findings show that adrenal corticosterone is involved in the regulation of schedule-induced wheel running.

Adrenal Glands

Sex differences in acetaldehyde on body temperature and open-field performance in the rat.

Using the open field, for making an overall assessment of behavioural change in response to acetaldehyde (AcH) treatment, the results from the present study demonstrate that AcH produces behavioural and physiological effects similar to those of ethanol. High doses of AcH produced a similar degree of change as high doses of ethanol. Both compounds render the animal incapable of locomotor activities, such as ambulation and rearing and both produce a decrease of 2-3 degrees C in body temperature. AcH, however, appears to be a much more potent compound as behavioural and physiological changes are exhibited even after a dose of 10 mg/kg, while the dose of ethanol necessary to produce a decrease in open-field behaviour is at least 10 times as much. Females were more sensitive to the effects of AcH at the 100 mg/kg dose.

Acetaldehyde

Mood state of heroin-dependent persons undergoing methadone detoxification.

A questionnaire (MSQ) was designed to evaluate subtle changes in subjective states accompanying methadone detoxification. A principal components analysis was applied to questionnaire data obtained from 29 male and female heroin-dependent persons at both moderate (42-22 mg) and low (21-1 mg) doses of methadone administration. Six factors were identified-a "schizophrenic" factor; general well-being; a mental outlook factor; a neurotic factor; a bipolar extroversion-introversion factor; a bipolar excitation versus euphoria-depression factor. A shift to a more negative mental attitude, and an increase in extroversion and excitability, was found with decrease in methadone dose.

Adult

Hormonal responses to a graded mental workload.

Three mental arithmetic tests of graded difficulty were presented to eight young male volunteers on consecutive days. The effort compensation patterns were investigated using urinary catecholamines and salivary cortisol. A significant increase in adrenaline excretion was found in response to all three tests. Urinary adrenaline was partially graded according to the level of difficulty of the tests. The response patterns to mental workload also included a significantly lower noradrenaline/adrenaline ratio and a higher adrenaline/dopamine ratio after the tests. No significant increase was found after the tests for noradrenaline and dopamine. Changes in salivary cortisol concentration during the tests were graded with respect to test difficulty between the easiest and both of the more difficult tests. Salivary cortisol concentration changes are proposed as the basis for field observations involving mental workload. It is concluded that mental workload causes distinguishable effort compensation patterns and that under certain conditions urinary adrenaline and salivary cortisol allow one to distinguish different mental workload levels.

Adult

Intravenous self-administration of phentermine in food-deprived rats: effects of abrupt refeeding and saline substitution.

The objectives in these experiments were to determine the effects on intravenous phentermine self-administration of abrupt refeeding and of saline substitution in food-deprived rats. In Experiment 1, 32 naive rats, reduced to 80% free-feeding weight (FFW), were assigned randomly to four equal-sized groups. Two groups self-administered phentermine, the other two saline over two consecutive six-day phases. In phase 1, all animals were maintained at 80% FFW, while in phase 2, one phentermine- and one saline-reinforced group was abruptly food satiated. Results showed that phentermine self-administration was suppressed. In Experiment 2, another 32 naive rats were assigned to four equal-sized groups and tested over two consecutive six-day phases. Two groups were FF, the other two were reduced to 80% FFW. In phase 1, a group of FF and 80% FFW animals self-administered phentermine, the other two saline, while in phase 2, treatments were reversed: previously phentermine-reinforced animals self-administered saline and vice versa. Findings showed that 80% FFW rats rapidly discriminate the introduction or removal of phentermine and alter responding accordingly, while FF animals respond at low rates throughout.

Animals

6-Hydroxydopamine and excitotoxin lesions of medial prefrontal cortex fail to affect schedule-induced drinking in the rat.

Schedule-induced drinking was examined in rats following 6-hydroxydopamine and N-methyl-D-aspartate lesions of the medial prefrontal cortex. 6-Hydroxydopamine reduced the concentrations of dopamine and noradrenaline in the medial prefrontal cortex to 17 and 37% of control values respectively, while changes were not observed in the nucleus accumbens. Lesions with N-methyl-D-aspartate were confined to the medial prefrontal cortex. Schedule-induced water consumption, determined over 11 consecutive 1 h/day testing sessions, was not significantly altered by either lesion. These results suggest that the mesocortical dopaminergic projection to the medial prefrontal cortex, and reciprocal projections from medial prefrontal cortex to the nucleus accumbens and the ventral tegmental area, are not essential for the acquisition of schedule-induced drinking.

Animals

Food deprivation fails to potentiate intravenous self-administration of fenfluramine in naive rats.

Recent findings show that in animals, i.v. self-administration of D-amphetamine, cocaine and phentermine, which act predominantly upon catecholamine (CA) containing neurons, is potentiated following chronic restricted feeding. The objective in this experiment was to determine whether food deprivation would potentiate self-administration of fenfluramine, an anorectic compound which acts predominantly upon serotonin (5HT) containing neurons. When saline and five doses of fenfluramine were made available for i.v. self-administration to naive free-feeding (FF) rats or food-restricted (FR) rats at 80% free-feeding weight, the rate of fenfluramine-reinforced responding did not differ significantly from saline-reinforced responding at any dose or deprivation state. These data suggest that the potentiation of responding which occurs under conditions of chronic restricted feeding is specific to compounds which act predominantly upon CA containing neurons.

Animals

Opiate-seeking behavior under conditions of methadone detoxification and removal.

This study was carried out to determine whether heroin-dependent persons, having completed methadone detoxification, can be maintained on an inert substance which has previously been associated with methadone. Forty heroin-dependent men and women were randomly allocated to either a "standard detoxification" group or a cordial substitution group. Results showed that subjects administered methadone-associated cordial after methadone detoxification could not be retained at the clinic for a time significantly beyond that of subjects in the standard detoxification group despite the inability of the subjects to accurately estimate methadone dosage. The role of cognitive factors is discussed.

Adult

Dopamine and salsolinol levels in rat hypothalami and striatum after schedule-induced self-injection (SISI) of ethanol and acetaldehyde.

Endogenous levels of salsolinol and dopamine were measured by a gas chromatography/mass spectrometry (GC/MS)--selected ion monitoring technique using deuterated internal standards in rats allowed to self-inject either acetaldehyde, ethanol or saline control solution over 20 days for 1 h/day. Significant increases in medial basal hypothalamic (MBH) and striatal salsolinol concentrations were found in animals exposed to acetaldehyde but not ethanol, whereas dopamine concentrations for these animals did not differ significantly from rats exposed to control conditions. The data provides further support for the in vivo formation of salsolinol following acetaldehyde exposure in experimental animals.

Acetaldehyde

Salsolinol and dopamine in rat medial basal hypothalamus after chronic ethanol exposure.

Endogenous levels of salsolinol and dopamine were measured by a gas chromatography/mass spectrometry (GC/MS) - selected ion monitoring technique using deuterated internal standards in Long Evans rats chronically exposed to ethanol for ten months. Chronic ethanol exposure produced significant increases of dopamine and salsolinol concentrations in the medial basal hypothalamus but not striatum. The data suggest that the occurrence of salsolinol in rat brain tissue is a consequence of an in vivo Pictet-Spengler cyclization.

Alcoholism

Phentermine self-administration in naive free-feeding and food-deprived rats: a dose response study.

In the present experiment graded doses of phentermine, an anorectic similar to amphetamine in structure and mechanism of action, were made available to naive free-feeding (FF) or 80% free-feeding weight (FFW) rats for IV self-administration. Findings showed that, in 80% FFW rats, the number of injections taken were an inverted U-shaped function of dose, whereas the amount of drug injected was a monotonically increasing function of dose. FF animals, however, failed to self-administer phentermine at rates that differed significantly from FF animals self-administering saline. These data suggest that the clinical use of anorectics which have a mechanism of action similar to amphetamine may increase the risk of drug dependence whenever weight loss is achieved.

Animals

Self-administration of low-dose cocaine by rats at reduced and recovered body weight.

Food deprivation significantly increases self-administration of cocaine in both rats and rhesus monkeys. The objective in the present investigation was to determine the effects of varying deprivational states on the level of IV low-dose (0.1 mg/kg/infusion) cocaine self-administration in rats. In the first experiment, 32 naive rats were assigned randomly to four equal-sized groups. Two groups self-administered cocaine, the other two saline over two consecutive 10-day phases. Across phase 1 all animals were free-feeding (FF), while in phase 2, one cocaine- and one saline-reinforced group were subjected to restricted feeding until they reached 80% free-feeding weight (FFW). Results showed that cocaine-reinforced responding was related inversely to body weight. In experiment 2 another 32 rats, reduced to 80% FFW, were assigned to four equal-sized groups. Two groups self-administered cocaine, the other two saline over two consecutive 10-day phases. Across phase 1 all animals were maintained at 80% FFW, while in phase 2, one cocaine- and one saline-reinforced group were abruptly food satiated. Findings showed that cocaine-reinforced responding decreased rapidly to low levels. Finally, the group of cocaine-reinforced rats maintained at 80% FFW across both phases of experiment 2 were also abruptly food satiated. Again, responding decreased rapidly to low levels.

Animals

Effects of acute food and/or water deprivation on muricide.

The present experiment was designed to test certain predictions derived from models of interactions between muricide and appetitive behaviors proposed earlier by Russell and Singer [8,9]. One of the major features of the models centered on whether the two types of behavior are inevitably related. The general design of the present experiment involved testing for muricide either (a) after deprivation of food and/or water or (b) at times during the normal diurnal cycle when the two consummatory responses were at their minima and maxima. Deprivation and testing for muricide were limited to a single episode in order to eliminate confounding effects of repeated deprivations and of repeated exposures to prey. Periods of acute deprivation ranging from 5.5 to 22.0 hr did not induce significant quantitative changes in muricidal behavior. However, muricide and the appetitive behaviors did co-vary under conditions associated with the normal diurnal cycle. Comparing the present results with findings from experiments using repeated deprivation leads to the suggestion that covariation of appetitive and muricidal behaviors is not an innate characteristic, but rather is acquired through processes of learning. Present results further suggest that each of the two types of behavior has its own physiological substrate which can be modified independently, but also may be activated concomitantly by a common set of antecedent conditions.

Aggression

Self-administration of phentermine by naive rats: effects of body weight and a food delivery schedule.

Food deprivation has been shown to increase intravenous self-administration of amphetamine and cocaine. In the present experiment, the response rates of four groups of eight rats for intravenous infusions of phentermine under free-feeding (FF) and 80% free-feeding weight (FFW) conditions in the presence and absence of a fixed time 1 min (FT-1) food delivery schedule, were compared with those of saline reinforced animals under identical conditions. The findings showed that: (1) Overall, response rates of phentermine-reinforced animals were significantly greater than were those of saline-reinforced animals; (2) 80% FFW animals self-injected significantly greater amounts of phentermine than did FF animals; and (3) the operation of an FT-1 schedule failed to affect the rate of phentermine-reinforced responding.

Animals