Search PubMed⌕ Search

Biomedical subjects

S F Leibowitz

Publications and source records attributed to S F Leibowitz.

At least 163 records · Page 9Linked to original sources
PubMed1978

Analysis of feeding suppression produced by perifornical hypothalamic injection of catecholamines, amphetamines and mazindol.

The effects on feeding of perifornical hypothalamic injection of catecholamines, amphetamines and mazindol were examined in hungry rats. In pargyline-pretreated subjects, both dopamine and epinephrine significantly suppressed food intake, at doses as low as 31 ng for dopamine and 150 ng for epinephrine (the latter injected with an alpha-adrenoceptor blocker). This effect was reliably strengthened by inhibiting catecholamine deamination or presynaptic catecholamine uptake. Perifornical injections of amphetamine, mazindol, methamphetamine, and phenmetrazine also suppressed feeding. The magnitude of this effect in individual animals was positively correlated with the effect produced by catecholamine agonists. Moreover, this effect of mazindol was partially antagonized by perifornical injection of dopaminergic and beta-adrenoceptor blockers. The effects of amphetamine and epinephrine were abolished by these drugs, while dopamine's effect was selectively inhibited by the dopaminergic antagonist. Serotonergic antagonists produced no change. These findings lend support to the hypothesis that perifornical hypothalamic catecholamine neurons, through dopaminergic receptors and beta-adrenoceptors, are involved in inhibiting feeding behavior, as well as in mediating the anorexic action of the amphetamines and mazindol.

Amphetamines↗
PubMed1978

Effects of para-chlorophenylalanine and 5-hydroxytryptophan on mouse killing behavior in killer rats.

The effects of para-chlorophenylalanine (PCPA) on mouse killing behavior were examined in natural killer rats. Forty-eight hr after injection, this serotonin synthesis inhibitor, at relatively low doses of 75 and 150 mg/kg, facilitated mouse killing, as indicated by a decrease in latency to attack the mouse. This effect was revealed in a test of satiation, in which five successive mice were presented to the rat, and also in a novel cage situation. Other than the shorter latencies to attack and kill mice, the killing response was similar in topography to the natural kill. The increase in killing after PCPA injection was associated with a reliable reduction in brain serotonin and in 5-hydroxyindoleacetic acid, and the time courses of the behavioral and biochemical changes were generally similar. In contrast to PCPA, injection of the serotonin precursor 5-hydroxytryptophan (5-HTP, 100 mg/kg) reliably lengthened attack and kill latencies in killer rats. In rats pretreated with PCPA, 5-HTP not only reversed this drug's facilitation of killing, but completely blocked killing in 67% of the rats tested. These results strengthen the hypothesis that brain serotonergic neurons are involved in the inhibition of mouse killing.

5-Hydroxytryptophan↗
PubMed1978

Paraventricular nucleus: a primary site mediating adrenergic stimulation of feeding and drinking.

Central injection of norepinephrine (NE) has been found to elicit preprandial drinking and feeding responses in the satiated rat. In the present study, 35 different brain areas, in over 500 rats, were examined to localize the precise region of NE sensitivity. Essentially all sites outside the hypothalamus, as well as in the lateral portion of the hypothalamus, were relatively or totally unresponsive to NE. In the medial hypothalamic area, the paraventricular nucleus (PVN) was clearly distinguished as the most effective site for initiating both feeding and drinking with noradrenergic activation in the satiated animal. Sites greater than 0.5 mm rostral, caudal, dorsal, ventral or lateral to this nucleus yielded significantly smaller effects. In mildly hungry rats, NE was found to potentiate the ongoing feeding response, and anatomical analyses of this phenomenon showed the PVN to be most responsive, with a smaller but reliable potentiation occurring along the periventricular hypothalamus adjacent to the third ventricle. Norepinephrine injected into the lateral perifornical hypothalamic area actually produced a suppression of feeding in these hungry animals. These findings, together with results from other studies, converge on the medial PVN region as being a key link in the process of increased food and water consumption associated with increased noradrenergic activity.

Animals↗
PubMed1975

Catecholaminergic mechanisms of the lateral hypothalamus: their role in the mediation of amphetamine anorexia.

The brain mechanisms mediating amphetamine's suppressive effect on feeding behavior were analyzed in rats with chronically implanted brain cannulas. Experiments in which drugs were injected directly into the anterolateral hypothalamus, the region found to be most responsive to amphetamine's action, yielded the following results. (1) Over a dose range of 6.25 nmoles (0.8 mug) to 400 nmoles (51.4 mug), hypothalamically injected D-amphetamine produced a reliable suppression of food consumption (20 percent at 6.25 nmoles, increasing to 88 percent at 200 nmoles) and was found to be approximately 3 times as potent as L-amphetamine in yielding this effect. (2) The anorexic effect of hypothalamically injected D-amphetamine was totally abolished by local administration of alpha-methyltyrosine, an inhibitor of dopamine, norepinephrine, and perhaps epinephrine synthesis, or by local administration of Fla-63, an inhibitor of only norepinephrine, and perhaps epinephrine, synthesis. (3) This effect of hypothalamic D-amphetamine was also antagonized by locally administered dopaminergic or beta-adrenergic receptor blockers but was unaffected by alpha-adrenergic, serotonergic, and cholinergic blockers. (4) Lateral hypothalamic administration of dopaminergic or beta-adrenergic receptor blockers, at quite low doses, was also effective in antagonizing the anorexia induced by peripherally administered D-amphetamine. These results strongly suggest that amphetamine, in suppressing feeding behavior, acts through the lateral hypothalamus, perhaps the anterior region, causing a release of dopamine and norepinephrine (or perhaps epinephrine) from lateral hypothalamic nerve endings and a subsequent stimulation of dopaminergic and beta-adrenergic receptors located in that region.

Amphetamine↗
PubMed1975

Pattern of drinking and feeding produced by hypothalamic norepinephrine injection in the satiated rat.

Injection of norepinephrine into the perifornical region of the anterior hypothalamus elicited both drinking and feeding in satiated rats. Analysis of these behaviors revealed the following: (1) Both responses were dose-dependent, occurring at doses at least as low as 0.5 mug. (2) The drinking response (1-4 ml) had a latency of around 1.5 min and a duration of 2-3 min. It was followed within a minute or two by eating (2-4 g) that lasted approximately 20 min. It was also followed by a period of drinking suppression that lasted approximately 60 min. (3) Satiation from the ingestion process appeared to be a primary factor in terminating the elicited feeding response, whereas a time-related factor was important in terminating the elicited drinking. (4) These ingestive responses produced by noradrenergic stimulation of the anterior perifornical hypothalamus were found to bear striking similarities to the rat's natural feeding behavior and premeal component of his natural food-associated drinking behavior. (5) These noradrenergically elicited responses could not be observed with lateral hypothalamic stimulation, while only feeding was elicited by ventromedial hypothalamic stimulation. (6) The drinking induced by central noradrenergic stimulation, in contrast to that induced by peripheral beta-adrenergic stimulation, was unaffected by nephrectomy.

Animals↗
PubMed1975

Ingestion in the satiated rat: role of alpha and beta receptors in mediating effects of hypothalamic adrenergic stimulation.

Anterior perifornical hypothalamic injection of l-norepinephrine in satiated rats elicits a brief, vigorous drinking response followed within a minute or two by a vigorous feeding response. These adrenergically elicited responses, which bear striking similarities to a rat's naturally motivated ingestive behaviors, were examined in the present series of experiments. It was found that: (1) Both responses could be elicited by perifornical hypothalamic injection of l-epinephrine, which was actually found to be more potent than l-norepinephrine. In contrast, only feeding could be elicited by the alpha-stimulant metaraminol, and neither feeding nor drinking could be elicited by hypothalamic injection of d-norepinephrine. l-isoproterenol, or dopamine. (2) The threshold doses of l-epinephrine for eliciting reliable ingestive responses were quite low, namely, 0.8 nmole (0.15 mug) for drinking and 0.2 nmole (0.04 mug) for feeding. (3) Pharmacological analysis of the ingestive behaviors induced by l-norepinephrine or l-epinephrine indicated that the eating response was mediated by alpha-adrenergic receptors, whereas the drinking response involved the synergistic action of both alpha- and beta-adrenergic receptors. No evidence for the involvement of dopaminergic or cholinergic (muscarinic) receptors was obtained. (4) A third adrenergically elicited phenomenon, namely, a suppression of drinking, was observed during and after the period of induced feeding. Analysis of this effect revealed its dependence solely upon alpha-adrenergic receptor activity.

Animals↗
PubMed1971

Hypothalamic alpha- and beta-adrenergic systems regulate both thirst and hunger in the rat.

Adrenergic and adrenolytic drugs were injected directly into the hypothalamus of the rat brain through permanently implanted cannulas and were found to have reliable effects on water consumption in water-satiated and water-deprived subjects. The beta-adrenergic agonist stimulated thirst, and the beta-adrenergic blocker suppressed thirst. Conversely, the alpha-adrenergic agonist suppressed thirst, and the alpha-adrenergic blocker enhanced thirst. These results demonstrate the existence of a hypothalamic beta-adrenergic "thirst" system which opposes a hypothalamic alpha-adrenergic "water-satiety" system. In view of our earlier results demonstrating the existence in the hypothalamus of an alpha-adrenergic "hunger" system which opposes a beta-adrenergic "food-satiety" system, we suggest that a reciprocal inhibitory relationship between these adrenergic hunger- and thirst-regulating systems provides a neurochemical explanation for the ability of organisms to maintain food and water consumption at a constant ratio. In the regulation of both hunger and thirst, the central cholinergic system mimics the hypothalamic beta-adrenergic system and opposes the hypothalamic alpha-adrenergic system.

Adrenergic alpha-Agonists↗
PubMed1970

Reciprocal hunger-regulating circuits involving alpha- and beta-adrenergic receptors located, respectively, in the ventromedial and lateral hypothalamus.

The injection of adrenergic and adrenolytic drugs directly into the brain through permanently implanted cannulas has yielded results showing that food consumption in the rat is regulated by a hypothalamic alpha-adrenergic "hunger" system. and a hypothalamic beta-adrenergic "satiety" system. The rats' differential responses to alpha-adrenergic and beta-adrenergic drugs injected into different hypothalamic sites indicate the following: (1) the lateral hypothalamic "feeding" center contains beta receptors, the activation of which produces satiation, presumably by inhibition of the lateral "feeding" cells; (2) the ventromedial hypothalamic "satiety" center contains alpha receptors, the activation of which produces eating, presumably by inhibition of the ventromedial "satiety" cells; and (3) the medio-lateral perifornical area of the hypothalamus contains both alpha and beta receptors, which lead to inhibition of the ventromedial or lateral hypothalamic centers respectively. It is suggested that the ventromedial and lateral hypothalamus are connected by reciprocal circuits, so that activation of the ventromedial center results in stimulation of the lateral beta receptors which inhibit the lateral "feeding" cells, and activation of the lateral center results in stimulation of the ventromedial alpha receptors which inhibit the ventromedial "satiety" cells.

Adrenergic alpha-Agonists↗
PubMed1969

Unexpected adrenergic effects of chlorpromazine: eating elicited by injection into rat hypothalamus.

Although chlorpromazine is believed to block adrenergic transmission, injection of this drug into the hypothalamus of satiated rats does not block norepinephrine-elicited eating, but instead mimics norepinephrine by eliciting eating. The amount of eating elicited by norepinephrine and by chlorpromazine is reliably correlated. These results suggest that endogenous norepinephrine mediates eating elicited by centrally injected chlorpromazine.

Animals↗
PubMed1966

Amnesia or reversal of forgetting by anticholinesterase, depending simply on time of injection.

The effect of intracerebral injections of the anticholinesterase drug diisopropyl fluorophosphate in rats was to produce good recall of an otherwise almost forgotten habit learned 28 days before. The same injections produced temporary amnesia for the same habit, otherwise well remembered, learned 14 days before. The injections had no ef fect on the memory of the same habit when it was only partly learned 14 days before. The results support the hy pothesis that the physiological basis of memory lies in an increase, and for getting in a decrease, in synaptic con ductance.

Amnesia↗