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Biomedical subjects

A J Zolovick

Publications and source records attributed to A J Zolovick.

At least 19 recordsLinked to original sources

Fenfluramine anorexia: a peripheral locus of action.

In a series of feeding pattern studies, amphetamine was shown to produce a period of complete anorexia often followed by a broken nibbling pattern of eating. Fenfluramine produced a regular feeding pattern in which a depressed meal size was not compensated for by an increase in meal frequency. The disproportionate lengthening of the post-meal interval relative to meal size was accompanied by a decrease in the rate of gastric emptying. Fenfluramine was most effective in lengthening post-meal interval when administered immediately after a meal, and was progressively less effective when the injection was delayed, allowing time for gastric emptying to occur. Amphetamine was shown to have similar but less pronounced effects, corresponding to its weaker effects on gastric emptying. Midbrain raphe lesions that abolished the fenfluramine effect on short-term intake of food-deprived rats did not attenuate fenfluramine's effect on gastric emptying, nor did the lesions attenuate the anorectic effect of fenfluramine on ad lib food intake. Lateral intracerebroventricular administration of fenfluramine not reduce feeding. These results suggest that fenfluramine controls feeding primarily by short-term signals related to food in the upper gastro-intestinal tract.

Animals↗

An improved pharmacological procedure for depletion of noradrenaline: pharmacology and assessment of noradrenaline-associated behaviors.

A pharmacological procedure which initially depletes noradrenaline (NA), dopamine (DA) and 5-hydroxytryptamine (5-HT) but permits repletion of DA and 5-HT was used to evaluate the role of NA in feeding behavior and intracranial self-stimulation behavior. The rapid-onset 'reserpine-like' vesicular depletion drug RO 4-1284 reduced NA and 5-HT 99% and DA 90% in rat forebrain within 1 h after administration with complete repletion of all amines occurring within 6 to 12 h. Treatment with the dopamine-beta-hydroxylase inhibitor FLA-63 significantly reduced NA (maximum depletion 42%) but not DA or 5-HT over the 12 h period of evaluation. The two drugs together produced a specific depletion of NA. Forebrain levels of NA in subjects pretreated with FLA-63 then given RO 4-1284 0.5 h later were reduced to 2% of control values for 8 h while vesicular stores of DA and 5-HT were repleted 77% and 93%, respectively, within 8 h after administration. Selective depletion of NA, in this manner, reduced deprivation induced food intake and lateral hypothalamic self-stimulation.

2H-Benzo(a)quinolizin-2-ol, 2-Ethyl-1,3,4,6,7,11b-↗

The role of norepinephrine in feeding behavior.

When dopamine-beta-hydroxylase is inhibited with FLA-63 (10 mg/kg) free feeding behavior is disrupted in satiated rats. While the average number of meals taken was not different from vehicle injected controls, meal size was decreased 58% in the first 9 hr after treatment with FLA-63. In starved animals, FLA-63, when given alone, produced little effect on feeding behavior, even though norepinephrine depletion was in excess of 40%. When given in combination with RO4-1284 (5 mg/kg), a vesicular reuptake inhibitor, feeding was reduced to 16% of control intake and norepinephrine was specifically depleted 99%. Feeding was reliably reinstated in animals which received FLA-63 plus RO4-1284 with either dl-threo-DOPs, a metabolic precursor to NE, or direct intrahypothalamic injections of NE. These findings suggest that the feeding inhibition observed after treatment with FLA-63 plus RO4-1284 is due to disruption of transmission in brain NE systems. A non-anorectic dosage of L110-140 (3.73 mg/kg), a specific FLA-63. Taken collectively, these findings suggest that the primary role of NE in feeding is maintenance of the consummatory response and that these effects are expressed in relation to activity in other neurochemical systems.

2H-Benzo(a)quinolizin-2-ol, 2-Ethyl-1,3,4,6,7,11b-↗

Cholinergic modulation of separation distress in the domestic chick.

The effects of nicotine, carbachol, hexamethonium and scopolamine were investigated on distress vocalizations (DBs) of acutely isolated domestic chicks. Nicotine attenuated, while the antimuscarinic scopolamine increased the frequency of separation-induced DVs. Furthermore, the stress attenuating effects of nicotine were blocked by pretreatment with scopolamine. These results implicate muscarinic receptor participation in the control of separation-induced distress, and support the suggestion that nicotine-induced DV suppression may result from activation of behaviorally relevant muscarinic receptors via central release of acetylcholine.

Animals↗

Opioid modulation of ingestive behavior.

Supportive evidence for an important role of endogenous opioid systems in modulation of ingestive behaviors is presented. Low doses of morphine (1.0-5.0 mg/kg) increase and low doses of naloxone (0.5-2.5 mg/kg) decrease food and water intake during both acute and chronic testing in mildly-deprived rats. Chronic infusions of naloxone with implanted osmotic mini-pumps elicited sustained dose-related suppression of food, water, and saccharin solution intakes but did not reduce ingestion of 10.0% glucose solution or food following 12 hr deprivation. Finally, naloxone treatment did not antagonize nocturnal ingestion of food any more than it reduced day time feeding when the latter was enhanced by prior food deprivation. These results indicate that an opiate agonist and an opiate antagonist modify ingestive behaviors oppositely, affirming that endogenous opioid systems may be involved in control of feeding and drinking. However, their role may be restricted to only indirect participation in homeostatic regulation via neural systems modulating emotional tone or goal-directed behaviors in general.

Animals↗

Some methodological problems in age comparisons of EEG sleep patterns for C57BL/6J mice.

Some methodological problems encountered in age comparisons of EEG patterns are discussed in the context of an analysis of open field activity scores before and after preparation for, and recording of EEG sleep patterns. Plasma corticosterone levels 11 days after surgery for EEG electrode implantation were also measured. Activity levels were modified more for three older than for a younger group of animals following surgery/recording sessions. Corticosterone levels were appreciably elevated for the oldest group of animals. The possibility was raised that procedures designed to allow recovery from post surgical shock and adaptation to electrode connections may result in disproportionate differences across age groups.

Age Factors↗

Electroencephalographic changes with age in male mice.

Electroencephalographic (EEG) changes, as measured by the awake state, slow-wave sleep (SWS), rapid-eye movement (REM) patterns and ratio of REM/total sleep, were recorded in aging male mice of DBA/2J and C57BL/6J strains. Results indicate that there is a significant increase in the awake state accompanied by significant decrease in SWS with advancing age for both strains, although these changes appear more pronounced in DBA/2J mice than C57BL/6J mice. Of considerable significance is the finding that REM sleep is absent in mice of DBA/2J strain at 23.5 months of age. Based on these findings, the conclusion was reached that strain DBA/2J ages significantly faster than C57BL/6J. The difference in aging between the two strains emphasizes the need for additional studies dealing with genetic aspects of aging.

Aging↗