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M A Marrazzi

Publications and source records attributed to M A Marrazzi.

12 recordsLinked to original sources
PubMed1990

Atypical endogenous opioid systems in mice in relation to an auto-addiction opioid model of anorexia nervosa.

We have proposed that the atypical opioid system in the mouse may be representative of that in the anorexia nervosa patient and may account for a biological predisposition to the disorder. This is in the context of our auto-addiction model of anorexia nervosa in which endogenous opioids play a critical role in its etiology. Morphine activation of the endogenous opioid systems increases food intake and causes sedation in most species, including normal humans and rats. In contrast in BALB/C mice, morphine causes anorexia and hyperactivity, which we suggest may be true in the anorexia nervosa patient. A variety of atypical opioid systems have been demonstrated in different mouse strains, based on other responses. The present study examines these strains with reference to the responses relevant to our anorexia nervosa model. Three patterns are described--anorexia with hyperactivity (BALB/C and C57BL/6J mice), anorexia without hyperactivity (DBA/J mice), and a biphasic curve with hyperphagia at low doses and anorexia and hyperactivity at higher doses (CF-1 mice). Only female mice were used. These atypical opioid systems may reflect a spectrum of biological predispositions to the disorder. These strain differences may also provide useful correlations of the genetic determinants of various opiate responses and provide useful comparisons in characterizing the essential features responsible for the atypical responses.

Animals↗
PubMed1990

Effects of U50,488, a selective kappa agonist, on atypical mouse opiate systems.

We have proposed that endogenous opioids play a critical role in the etiology of anorexia nervosa, mediating an auto-addiction, and that atypical opioid systems in mice may be representative of those in anorexia nervosa patients, in contrast to normal humans and rats. A biological predisposition to eating disorders may result from these atypical opioid systems. Definition of these systems as atypical is based on their responses to morphine, which are preferential for the mu receptor subtype. Three patterns have been described in four strains of mice: anorexia with hyperactivity (BALB/C and C57BL/J), anorexia without hyperactivity (DBA/J), and a biphasic curve (CF-1). The latter showed anorexia and hyperactivity at high doses but increased food intake without a change in motor activity at low doses. These patterns contrast to the increase in food intake and sedation in typical species, including rats and normal humans. In the present study, U50,488, a selective kappa agonist, increases food intake in all four mouse strains, as previously reported in rats. Thus, these two agonists have opposite effects on the atypical mouse systems, but similar effects on the typical rat system. The typical and atypical opioid systems respond oppositely to morphine but similarly to U50,488.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1987

Atypical responses to morphine in mice: a possible relationship to anorexia nervosa?

According to our previously proposed auto-addiction hypothesis of chronic anorexia nervosa, patients become addicted to an initial period of dieting through endogenous opioid mediated mechanisms. Morphine causes hyperactivity and anorexia in the mouse, symptoms of anorexia nervosa but responses opposite to those of most species including rats and normal human subjects. This suggests that the atypical opioid systems in the mouse may resemble those of the chronic anorexia nervosa patient in contrast to those of most species including the normal human. Characterization of this atypical opioid system may be useful in understanding the pathophysiology of anorexia nervosa.

Animals↗
PubMed1986

Effects of thioglucoses on sensitivity to insulin hypoglycemic convulsions.

Based on the effects of gold thioglucose (GTG), we have previously proposed a regulatory center in brain which adjusts the convulsive response to insulin hypoglycemia. The sensitivity to insulin hypoglycemic convulsions is decreased 24 hr and increased 1 week after a single i.p. injection of GTG. The differences are in the brain's convulsive response to equal hypoglycemia, as the blood glucose response to insulin is unchanged. The generalized convulsive threshold, reflected in the sensitivity to nonmetabolic pentylenetetrazol (Metrazol) convulsions, is not altered. Despite its systemic administration, GTG causes lesions focused in the ventromedial hypothalamus. In the present study, this regulatory center was explored further by the ability of two thioglucoses to substitute for GTG. beta-D-Thioglucose had no effect. 5-Thioglucose simulated the early (24 hr) action of GTG but had no effect at 1 week. However, unlike GTG, 5-thioglucose did not cause the ventromedial hypothalamus lesion. The early (24 hr) and late (1 week) components are thus dissociated. The early effect on insulin hypoglycemic convulsions does not require a ventromedial hypothalamus lesion. Structure-activity relationships and relationships to glucoregulatory systems are discussed.

Animals↗
PubMed1985

Thioglucose interactions with a "gold thioglucose-lesioned glucostat".

Our previous studies suggest a central nervous system regulatory center that adjusts the brain's convulsive response to the insulin hypoglycemia based on decreased sensitivity to insulin hypoglycemic convulsions 24 hr after a single i.p. injection of gold thioglucose (GTG). This decrease is a change in the convulsive response to equal hypoglycemia and is not a change in the generalized convulsive threshold. GTG simultaneously causes a cytotoxic lesion focused in the ventromedial-arcuate hypothalamus (VMH), and the proposed regulatory center may be thought of as a "GTG-lesioned glucostat." However, 5-thioglucose (5TG) substitutes for GTG in decreasing the sensitivity to insulin hypoglycemic convulsions but does not lesion the VMH. In the present study, two possible explanations were explored for this previously reported dissociation of the 5TG functional effect and the VMH lesion. First, an interaction of 5TG with the GTG-lesioned glucostat in the VMH, without itself causing a lesion, was not supported by competition experiments, i.e., GTG lesion formation was not inhibited by appropriate 5-TG pretreatment. beta-D-Thioglucose, for which the sulfur substitution is more like GTG, is also compared. Two indices of GTG lesion formation were used, histology and the increased body weight that eventually results from a VMH lesion. Second, no 5-TG-induced lesion was found anywhere in the brain. Thus, no support was found for the possibility that 5-TG and GTG share a common lesion at some site other than the main VMH lesion of GTG. Other explanations must be sought.

Animals↗
PubMed1977

Intracellular recording of cerebral cortical actions of prostaglandins F2alpha (PGF2alpha).

Our reported data on the cortical inhibitory actions of prostaglandin F2alpha (PGF2alpha) and the diversity of data in the literature on cerebral PG actions are examined here in the light of intracellular recording which provides the requisite membrane data for the first time. Thus, 1) intracellular recording from the cat cerebral cortex is obtained for the actions of PGF2alpha and for norepinephrine (NE) and serotonin (5HT). 2) The parallel changes in firing and polarization and the simultaneous transmembrane conductance changes are qualitatively identical for PGF2alpha, NE and 5HT. 3) The reduction in firing accompanied by hyperpolarization indicates that PGF2alpha, NE and 5HT all inhibit these cells. 4) The ionic species responsible for this inhibition is such that it increased the transmembrane resistance, and this was true for all three. 5) The changes in membrane parameters, identical in direction for PGF2alpha and NE, but stronger for the latter, constitute conditions that can lead to competitive inhibition and therefore connote, presumably, actions at the same or related receptors. Such competition with evoked cortical field potentials is shown in the preceding paper.

Animals↗
PubMed1977

Effects of prostaglandin F2alpha on cerebral cortical evoked potentials.

The cerebral cortical action of prostaglandin F2alpha (PGF2alpha) has been determined by recording the effects of intracarotid injections of PGF2alpha on cerebral evoked potentials. PGF2alpha differentially reduced cortical evoked potentials. The cortical action of PGF2alpha appeared to be qualitatively identical with that of norepinephrine (NE) but weaker. A protection of the cortex from the inhibitory action of NE by a preceding dose of PGF2alpha was demonstrated. The actions of both PGF2alpha and NE appear to be on the same or related postsynaptic receptors. The actions described were at doses that did not reduced oxygen availability. PGF2alpha may act as a modulator of adrenergic transmission in the cortex. The intracellular recording in the companion paper supplies the further critical evidence that PGF2alpha has a synaptic inhibitory action.

Animals↗