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Biomedical subjects

G Singer

Publications and source records attributed to G Singer.

At least 55 records · Page 3Linked to original sources
PubMed1984

Self-injection of diazepam in naive rats: effects of dose, schedule and blockade of different receptors.

The present series of experiments had two main objectives: The first was to determine the conditions under which self-injection of the benzodiazepine diazepam would be optimal; the second was to identify neurochemical substrates which underlie the maintenance of diazepam self-administration. Data from the first experiment indicated that rats maintained on an FI-1 (Fixed Interval of 1 min) schedule of food delivery self-injected significantly more diazepam than rats not maintained on this schedule. Results from the second experiment demonstrated that the benzodiazepine antagonist Ro 15-1788, and the GABA antagonist bicuculline, significantly reduced diazepam self-administration, but the opiate antagonist naloxone was without effect. Data from the third experiment showed that the dopamine antagonist haloperidol also significantly reduced the rate of diazepam self-injection. Thus, these findings indicate that the acquisition of diazepam self-injection occurs under an FI-1 schedule of food delivery, which has been shown to be middly stressful, while its maintenance depends upon the functional integrity of benzodiazepine and GABA receptors and upon the activity of dopaminergic pathways.

Animals↗
PubMed1984

Urinary dopamine in physical and mental effort.

Dopamine in urine was investigated during three levels of physical stress (at 35%, 50%, and 75% VO2 max.) and three kinds of mental stress (delayed auditory feedback, vigilance task and arithmetic task). A statistically significant increase in excretion of dopamine was found in response to physical exercise and the delayed auditory feedback test. The response patterns (ratios noradrenaline/dopamine and adrenaline/dopamine) after physical and mental stress differed. The data presented support the possibility of using dopamine excretion and the above ratios to differentiate between mental and physical effort.

Adult↗
PubMed1984

Effects of naloxone and buprenorphine on intravenous acetaldehyde self-injection in rats.

Rats can be induced to self-inject acetaldehyde under an appropriate operant conditioning schedule. The narcotic antagonist naloxone (30 mg/kg) is shown to produce a decrease in schedule-induced acetaldehyde self-injection, but was without effect on both barpress responding and spontaneous activity in rats tested individually for fine, gross and total activity. On the other hand buprenorphine (0.3 and 3 mg/kg), the mixed agonist-antagonist derived from the opium alkaloid thebaine, also produced a significant decrease in acetaldehyde self-injection. However, a significant effect of buprenorphine on barpressing in otherwise drug naive rats indicated that this finding should not be dissociated from a possible involvement of buprenorphine on motor responding. While the findings are consistent with the hypothesis of opiate involvement in acetaldehyde self-administration, caution must be exercised when drawing conclusions about the participation of endogenous opiates in acetaldehyde-mediated behavior.

Acetaldehyde↗
PubMed1984

Effects of 6-OHDA lesions in the nucleus accumbens on the acquisition of self injection of heroin under schedule and non schedule conditions in rats.

Acquisition of heroin self injection is enhanced in bodyweight reduced rats if a non contingent food delivery schedule is operating (schedule-induced self injection). Dopamine depletion of the nucleus accumbens septum (NAS) reduces nicotine self injection and a number of other schedule-induced behaviours. In the present experiment 6-OHDA lesions in the NAS significantly reduced the levels of heroin self injection in 7 rats on a food delivery schedule compared with sham lesioned controls. The reduced heroin intake did not differ from that of lesioned or sham lesioned rats with no schedule present. The results confirm previous reports that intact dopaminergic neurones in the NAS are necessary for schedule-induced behaviours to occur, and demonstrate that components of the same behaviour which are not schedule-induced can continue without disruption in the presence of the lesions.

Animals↗
PubMed1984

Resistance of schedule-induced behaviours to hippocampal lesions.

It has been reported that electrolytic lesions of the hippocampus accelerate the onset of schedule-induced drinking (SID) and also lead to significant increases in adrenal weights [2]. In the present experiment three groups of Long Evans rats received electrolytic or 6-Hydroxydopamine or sham lesions of the hippocampus and one group received electrolytic cortical lesions. Half of each group were tested 1 hr/day for 10 days under scheduled food delivery and the other half received food in a single presentation. It was found that both electrolytic hippocampal and cortical lesions reduced the level of SID compared with sham and 6-Hydroxydopamine lesions which did not differ from each other. However, there is support for the suggestion that hippocampal catecholamine neurones are involved in corticosterone regulation as shown by a significant increase in plasma corticosterone levels in non-scheduled, 6-Hydroxydopamine lesioned rats.

Animals↗
PubMed1984

Cortisol and catecholamines changes as functions of time-of-day and self-reported mood.

Six male graduate students, unrestricted in their lifestyle, collected their own urine over a seven-day period: it was analysed for cortisol, noradrenaline, adrenaline and dopamine. At each urination subjects self-assessed their mood. On two separate days, blood samples were collected at 4-hourly intervals for plasma cortisol assay. Mean plasma cortisol levels showed the expected circadian variation, but two subjects had divergent patterns. Mean urine cortisol accumulation also showed circadian variation with a 2-4 hour lag behind plasma values. Mean urine catecholamine levels showed both time of day and considerable individual variation. A statistical procedure, involving comparison of two models, was developed to determine differences between subjects' excretion patterns. An underlying common pattern of cortisol and catecholamines excretion was found. Regression of hormone levels against self-assessed mood changes revealed correlations of (1) adrenaline accumulation with physical fatigue, (2) cortisol with alertness and (3) ratios of adrenaline, noradrenaline and dopamine with tenseness and irritability.

Adult↗
PubMed1984

Relationships between catecholamines in urine and physical and mental effort.

Excretion of noradrenaline and adrenaline was investigated in two experiments which included 3 physical test sessions and 3 mental test sessions (Experiment X) and a week of real-life situations (Experiment Y). An increased excretion of both catecholamines was found during each test in Experiment X. The noradrenaline excretion discriminated well between physical and mental tests, but one i.e. 35% VO2max. Adrenaline excretion discriminated the arithmetic test (AT) from the other mental tests. The noradrenaline/adrenaline ratio (NA/A) separated the AT from all other tests. The different adrenergic response patterns to physical and mental effort were confirmed in the real-life situations. The NA/A ratio reflected these differences. It was over 5 for physical activities and between 2 and 3 for mental activities. The different response patterns allow one to differentiate between physical and mental effort.

Adult↗
PubMed1984

Schedule-induced self injection of drugs.

The schedule-induced polydipsia paradigm has been used to induce oral ingestion of large volumes of alcohol, barbiturate and other drug solutions. We have developed a method of schedule-induced self injection which allows the study of acquisition and maintenance of drug intake behaviour in changing environments free from the interference of taste factors or imbalances due to excessive water intake. In this paper we review our findings on the acquisition and maintenance patterns of amphetamine, methadone, heroin, alcohol, nicotine, cocaine, delta 9-THC and haloperidol . For all drugs except amphetamine, the combination of schedule and nutritional deprivation leads to the highest rates of drug intake although the schedule does not appear to be a potent factor at free feeding weight. Drug intake is the result of the interaction of environmental factors and pharmacological properties of the drugs, rather than the effects of drug or environmental factors separately . From a number of preliminary studies, data on corticosterone response in drug self-injection behaviour and the function of the nucleus accumbens septum are presented.

Alcoholism↗
PubMed1984

The effect of naloxone on schedule-induced and other drinking.

A dose-response study of the effect of naloxone on schedule-induced drinking confirmed that this type of drinking is resistant to the opiate antagonist at doses which depressed drinking induced by water-deprivation, hypertonic saline and salbutamol. Naloxone also failed to reduce intake of saline solution in the presence of scheduled food presentation. The findings support the suggestion that schedule-induced drinking is regulated by a system of neural control which differs from that involved in deprivation and other forms of drinking. It would appear that opiate receptors do not play a part in the regulation of schedule-induced drinking.

Albuterol↗
PubMed1983

Copper salicylate as an anti-inflammatory and analgesic agent in arthritic rats.

Recent research indicates that endogenous copper is involved in anti-inflammatory and tissue repair processes. Of interest also is the analgesic efficacy of Cu complexes, since rheumatoid arthritis and similar inflammatory conditions are extremely painful. In pilot experiments, arthritic rats failed to increase voluntarily their rate of drinking a 5 mg/ml solution of copper salicylate (Cu Sal). The data from the experiment reported here showed that a forced oral dose of Cu Sal calculated at 200 mg/kg body weight significantly reduced sensitivity to mechanical pressure in less than 30 minutes but more than 15 minutes. The analgesic effect of the Cu Sal was greater for arthritic than for non-arthritic rats, suggesting that two types of analgesia are involved. First, it produces a direct analgesic effect which works irrespective of the presence of inflammation. Second, it appears to have an indirect analgesic effect due to reduction of inflammatory hyperalgesia. It was also found that Cu Sal administered orally reduces inflammation in rats with adjuvant arthritis. In summary, the results from this experiment demonstrate that Cu Sal has specific and general analgesic properties and anti-inflammatory potential.

Administration, Oral↗
PubMed1983

The 'direct' pharmacological effects of heroin on operant responding and activity: the yoked-operant procedure.

The present study demonstrates a method which enables separation of the 'direct' pharmacological effects of heroin on activity and operant responding from the 'indirect' reinforcing effects of heroin. Experiment I was carried out at 0.1 mg/kg heroin with naive male albino Wistar rats (N = 21) from a La Trobe University (Bundoora, Australia) colony. Experiments II and III were carried out at 0.05 mg/kg (N = 21) and 0.2 mg/kg (N = 21) heroin doses with Wistar rats from a Monash University (Clayton, Australia) colony. Each experiment consisted of a 5-day pre-training period and a 10-day experimental period. Food-contingent operant behaviour was shaped in 14 animals during the first 4 days of the pre-training period. On day 5, baseline data was taken. Pairs of animals were then randomly yoked to one of seven naive 'executive' animals and the executive animals were allowed to self-inject heroin. Each self-injection of heroin by an executive animal led to a simultaneous injection of heroin to a yoked-heroin animal, and a simultaneous injection of saline to a yoked-saline animal. Results of 1-h data showed a significant decrement in food-contingent operant behaviour only for the yoked-heroin animals in the 0.2 mg/kg and 0.05 mg/kg groups. A significant decrement in both food-contingent operant behaviour and activity was found for the yoked-heroin animals at all three doses studied when data from the first half of 1-h sessions only was examined. It was concluded that the rate of self-injection demonstrated by executive animals was limited by the direct pharmacological effects of heroin on activity, and that the impairment of responding for food reflected this direct pharmacological effect of heroin. A theoretical model of reinforcement strength was subsequently proposed.

Animals↗
PubMed1983

Relations between muricide, circadian rhythm and consummatory behavior.

Three forms of behavior--muricide, eating, and drinking--have been studied at six photic periods during a 12/12 hr light/dark circadian cycle to which the subjects have been habituated. One hundred and eight rats served as subjects, 18 per photic period. The frequency of muricide was recorded for each period and subsequent food and water intakes were measured during a 1 hr test period. Results show a significantly higher frequency of muricide during the dark than during periods of light. Food intake covaried significantly with the incidence of muricide rs = 0.89, p less than 0.05), while no such relationship was found between muricide and water intake (rs = 0.17, p less than 0.05). The findings are consistent with reports of circadian changes in other rodent behaviors, including rhythmicity in home-cage and in shock-induced aggression. Covariation of muricide and eating does not establish a causal relation between the two. Three models of physiological mechanisms which might provide substrates for the covariance are discussed.

Aggression↗
PubMed1983

The effects of alcohol induced malnutrition in pregnancy on offspring brain and behavioral development.

Alcohol is known to have various deleterious effects in all animals including man. The present study was designed to establish whether the effects of moderate EtOH intake during pregnancy on offspring are due to toxic effects of the substance or to nutritional changes; whether effects are long lasting or limited in duration; and whether effects are due to the prenatal action of the substance or effects persisting into the postnatal period. The findings show that the effects obtained in our study are due to malnutrition engendered in the prenatal period and are of limited duration. Since much evidence suggests that early deficits are difficult to compensate for, it is possible that the tests used with mature animals in this study may have been insensitive to residual deficits. Alternatively, rats may truly have compensated for early retardation. This does not necessarily imply that the same compensatory processes would apply in humans, where greater complexity of environmental demands is imposed from an early age.

Alcoholism↗
PubMed1983

The effect of 6-OHDA lesions of the nucleus accumbens septum on schedule-induced drinking, wheelrunning and corticosterone levels in the rat.

In a series of four experiments the relationship between 6-OHDA lesions of the nucleus accumbens septum (NAS), schedule-induced behaviors and plasma corticosterone levels was explored. Data from the first experiment show a significant decrease in water intake during a scheduled food delivery test hour for 6-OHDA lesioned groups of rats compared with sham or non-lesioned groups of rats, while during the remaining 23 hours of the day water intake was the same for 6-OHDA lesioned and sham lesioned groups. In a second experiment similar decreases in schedule-induced wheelrunning were observed for 6-OHDA lesioned rats when compared with sham lesioned rats. Data from a third experiment showed significant increases in plasma corticosterone levels of rats in the presence of a scheduled food delivery compared with rats given non-scheduled food. In a fourth experiment it was shown that 6-OHDA lesions of the NAS abolish this increase of corticosterone levels in rats on a food delivery schedule. These data extend the findings of Robbins and Koob [19] and show a more general involvement of the dopaminergic pathways of the NAS in schedule-induced behaviors and in concomitant plasma corticosterone changes.

Animals↗
PubMed1983

The suppression of ethanol self injection by buprenorphine.

The schedule induced self-injection procedure was used to establish ethanol self-injection in 16 rats. Pretreatment with an injection of 0.3 mg/kg buprenorphine significantly reduced ethanol self-injection in a group of 8 rats. This effect was not found in a second group of 8 rats which received saline pretreatment. The findings provide support for an involvement of buprenorphine, in ethanol self-injection, which cannot be explained in terms of opiate induced shifts in taste preference. From the present data it cannot be determined whether the agonist or antagonist opiate properties of buprenorphine cause the blocking effect.

Alcohol Drinking↗
PubMed1983

A reinterpretation of schedule-induced behaviors based on a systematic analysis of behavior.

Confusion exists regarding the criteria to be used in determining whether or not particular behaviors are schedule-induced. Four critical characteristics of schedule-induced behaviors are suggested and a comparison made of the complete range of behaviors exhibited by body weight-reduced rats drinking in response to one of three stimuli. These were (1) a fixed-time food reinforcement schedule, (2) a meal of dry food, and (3) 24 hour water deprivation. Drinking, locomotion, rearing and oral and perioral behaviors occurred in accordance with the defining characteristics of schedule-induced behaviors. Rats in the fixed-time reinforcement condition also deposited significantly greater numbers of fecal boli. Sniffing and food bowl related behaviors occurred as terminal responses for this group. It is concluded that animals which receive reinforcers intermittently maintain high levels of arousal for extended periods, and that the presence of the schedule may mimic conditions experienced by wild rats in non-laboratory settings. In such conditions ambulatory behaviors may be particularly adaptive. In contrast, reinforcing sensory feedback and a stress reducing role may be particularly important in the mediation of oral behaviors (such as drinking) which occur during intermittent reinforcement.

Animals↗
PubMed1983

Effects of interactions between amphetamine and food deprivation on covariation of muricide, consummatory behaviour and activity.

Four experiments were conducted to study covariation of muricide, consummatory behaviour and general activity under conditions involving interactions between food deprivation and anorexia induced by low doses of d-amphetamine. Two basic experimental designs were used: (a) dosage of amphetamine was varied, with duration of deprivation constant at 22 hr; and (b) deprivation was varied, with a constant amphetamine dose of 1.0 mg/kg body weight. In general, effects of both types of manipulation on eating, drinking, general activity, and muricidal behaviour were consistent with earlier reports of effects when either deprivation or amphetamine-induced anorexia was varied separately. Rank order correlations supported the conclusions that relations between muricide, eating behaviour and general activity were both dose and time dependent. However, there also was evidence that such covariations existed for some, but not all, parameters of these behaviours, eg. differences in the median effective doses of amphetamine; differences in threshold doses; and differences in durations of deprivation required to counteract effects of amphetamine. A dissociation of muricide and eating behaviour was strikingly evident when all satiated animals injected with normal saline engaged in muricidal behaviour and when increasing deprivation had no significant influence on carcass consumption or muricidal behaviour of saline treated subjects. The present results are interpreted as essentially inconsistent with concepts in which covariation of muricide and consummatory behaviour is considered to depend: (a) upon a common set of physiological conditions, or (b) upon one being the antecedent of the other. However, results are consistent with a model in which each behaviour has its own basic physiological condition(s) which may be activated concomitantly.

Aggression↗