Biomedical subjects
Publications and source records attributed to G Singer.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.
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The effect of amphetamine and l-dopa was compared in 22-hr food- and water-deprived rats. Amphetamine produced marked anorexia, and l-dopa significantly reduced food intake at 200 mg/kg. Following pretreatment with RO 4-4602, a decarboxylase inhibitor, 100 mg/kg of l-dopa, a dose that did not significantly affect eating, produced marked anorexia. The anorectic effect of both amphetamine and l-dopa was antagonized by propranolol, a beta adrenergic antagonist. Phentolamine, an alpha-adrenergic antagonist, potentiated the anorectic effect of amphetamine and l-dopa. Haloperidol (0.1 mg/kg), a dopamine antagonist, failed to prevent the anorexia due to amphetamine but accentuated that due to l-dopa. Methysergide, a serotonin antagonist, also failed to prevent the anorexigenic effect of amphetamine. Finally, the administration of l-dopa with or without peripheral decarboxylase inhibition resulted in more than twice the increase in hypothalamic dopamine levels without significant changes in 5-HT or norepinephrine levels. The data show that the anorexigenic effect of amphetamine and l-dopa are similar and indicate a functional role for both norepinephrine and dopamine neurons in feeding behaviour in the rat.
Intrahypothalamic injections of 3 doses of norepinephrine were administered to rats under conditions of 80 percent body weight reduction (prepolydipsia), 80 percent body weight reduction (schedule induced polydipsia), and normal body weight (postpolydipsia). The only significant reduction in water intake occurred with the highest dose of norepinephrine, under the prepolydipsic condition. The fact that norepinephrine failed to block schedule induced polydipsia indicates that this behavior is regulated by a different biochemical system than that of deprivation induced drinking.
Cannulas were stereotactically implanted in the lateral hypothalamus and the ipsilateral amygdaloid cortical nucleus of 7 male albino rats, Wistar strain. After functional checking of the accuracy of implants by adrenergic elicitation of increased food intake, the animals were injected with combinations of noradrenaline, phenoxybenzamine or tolazoline, or placebo under 6 treatment conditions, while food-and water satiated. The elicitation of increased food intake in the satiated rat by adrenergic stimulation of the lateral hypothalamus was confirmed, and it was further found that simultaneous adrenergic stimulation of the amygdaloid cortical nucleus augmented this increase. However, simultaneous anti-adrenergic blockade in the amygdaloid cortical nucleus reduced eating to control level. The lack of response of the amygdaloid cortical nucleus to adrenergic stimulation in the satiated rat, under simultaneous stimulation of the lateral hypothalamus with either placebo or an adrenergic blocker, was also demonstrated. It was concluded that the amygdaloid cortical nucleus has a modulatory influence on eating behavior, which is dependent on the level of activity in the lateral hypothalamus, and further that this modulatory influence is necessary to the behavioral output of the hypothalamic system. This is the same relationship between the hypothalamus and amygdala previously demonstrated in regard to drinking behavior and these results are seen as supporting the behavioral generality of the functional relationships reported.
Marked differences in extent of diffusion have been shown with the fluorescence histochemical method between guanethidine and 6-OHDA(64 mug in 2 mul) when injected acutely or chronically into the lateral hypothalamus, the substantia nigra or the amygdala of the rat brain. Cannulation damage up to 1 mm in diameter and attributed to the implantation of cannulae and placebo injection was observed. A further area of generalized damage occurred following the injection of drugs and was far greater for 6-OHDA (2 mm) than for guanethidien (0.3 mm). Guanethidine, but not 6-OHDA, caused specific damage to catecholamine-containing nerurons up to a distance of at least 3 mm and more from the cannula tip. These striking differences between the effects of intracranial injection of 6-OHDA and guanethidine are discussed in terms of the uptake and degradation of the two drugs and the anatomical features of the injection site; they are not explicable in terms of experimental conditions such as concentration, volume of injection, molecular weight or lipid solubility. The different patterns of damage would not easily be distinguished by biochemical analyses and the catecholamine specificity of 6-OHDA in studies of the central nervous system must be seriously questioned. Vascularization of chronically implanted cannula tracks and the presence of anatomical diffusion barriers are also discussed in relation to the diffusion of drugs injected intracranially.
Low (64 mug in 2 mul) or high 320-1280 mug in 2 mul) doses of guanethidine sulphate were injected daily for up to 19 days into the lateral hypothalamus, substantia nigra, locus coeruleus, dorsal raphe nucleus, or amygdala region of the rat brain. Effects on monoamine-containing neurons were determined using fluorescence histochemistry. The noradrenergic terminals of the hypothalamus were depleted over a diameter of 7 mm by both low and high doses of guanethidine whereas, even with high doses, the dopaminergic terminals of the median eminence, amygdala and acudate nucleus were only partially depleted. Fluorescence levels of dopaminergic cell bodies of the sub stantis nigra and 5HT-containing cell bodies of the dorsal raphe nucleus were unaltered by low doses of guanethidine. Low doses of guanethidine did not affect the fluorescence of the noradrenergic cell bodies of the locus coeruleus, however high doses caused a substantial reduction in fluorescence levels. Normal levels of fluorescence were observed in all catecholamine-containing neurons within 14 days from cessation of injections. Thus, the xon retraction and eventual degeneration of peripheral sympathetic adrenergic neurons, which occurs as a result of chronic intraperitoneal injections of guanethidine does not occur with the catecholamine-containing neurons in the central nervous system. The rapid recovery of centrat catecholamine-containing neurons is remarkable in view of the extensive areas of brain damage produced by chronic injection of such high concentrations of drug. Fluorescence in peripheral adrenergic nerves was unaffected by chronic injection of guanethidine into the lateral hypothalamus but adhesions of some internal organs were observed. Blood vessels in the vicinity of the cannula were heavily reinnervated by fluorescent fibres probably arising from intracranial catecholamine-containing neurons. Some of the advantages of intracranial injection of guanethidine compared to 6-hydroxydopamine for behavioral experiments are discussed.
Recent investigations have demonstrated the susceptibility of various components of the immune system to behavioral conditioning, using a conditioned taste aversion (CTA) paradigm. In Experiment 1 the effective antipyretic dose (40 micrograms/kg) and duration of antipyretic action (up to 4 hr) of alpha-melanocyte-stimulating hormone (alpha-MSH) was determined in rats tested with lipopolysaccharide (LPS). In the second experiment, alpha-MSH was used as the unconditioned stimulus (UCS) and paired with a novel-tasting saccharin solution (0.1%) to elicit a conditioned antipyretic response to a fever induced one hour previously by LPS. Both the antipyretic effect of alpha-MSH and the pyrogenic effect of LPS were found to be significantly conditionable. The conditioning of fever/antipyretic responses demonstrates for the first time that still another aspect of the host response can be influenced by conditioning procedures.
The lateral hypothalamic (LH) syndrome characterized by impairment of the ability to regulate food and water intake has been reported to occur after injections of 6-hydroxydopamine (6-OHDA) into this region. In the present experiment the fluorescence histochemical technique was used to assess monoamine depletion of noradrenaline and dopamine containing neurons following intrahypothalamic injection of 6-OHDA. Results show that the intensity and area of monoamine accumulation in axons served by 6-OHDA is correlated with the severity of behavioral deficits but that actual catecholamine depletion of either the corpus striatum or the hypothalamus is unrelated to the syndrome. Possible mechanisms of action of this accumulation in producing behavioral deficits are discussed.
The effects of intravenous acetaldehyde or saline self-injection and feeding regimes on oral alcohol consumption in rats was examined. The alcohol solutions offered to the animals was increased systematically in concentrations from 3 to 30%, according to a three-bottle, two-choice technique. Results suggest that (1) acetaldehyde pre-treatment using a self-injection procedure induces increased consumption of alcohol, the effect being particularly marked when coupled with conditions of food-deprivation (2) food-deprivation alone may be capable of inducing increased alcohol intake and this effect may persist even when deprivation is terminated (3) the combination of acetaldehyde and food-deprivation is most effective when food-deprivation follows a period of free-feeding. These findings provide support for an involvement of acetaldehyde in the development of an animal's preference for alcohol.
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Thirteen subjects were investigated to compare the effects of pre-event glucose (G) and placebo (P) ingestion on plasma free fatty acid (FFA) concentration during mental work. Subjects performed two trials of a videogame and received money for each point scored. Thirty minutes before commencing each trial, subjects ingested either a solution containing 50 g of G or an identically sweetened and colored placebo. Order of ingestion was partially counterbalanced. Heart rate, the measure of arousal monitored, increased significantly above baseline during each trial, but there was no difference in this rise between trials. The main finding from this experiment was that after ingesting glucose, subjects had a stable blood FFA concentration during the videogame, while after the ingestion of placebo subjects had a significantly higher blood FFA during videogames than they had at baseline. These data suggest that arousal-induced hyperlipidemia can be prevented by pre-event glucose ingestion.
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