Evidence that punctate intracerebral administration of 6-hydroxydopamine fails to produce selective neuronal degeneration

Butcher, Larry L.; Eastgate, Sheila M.; Hodge, Gordon K.

doi:10.1007/bf00499527

Cited by 110 publications

(5 citation statements)

References 39 publications

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“…The argument that catecholamine neurons are responsible, at least in part, for the obesity syndrome of the db/db mouse assumes that 6-OHDA is a specific neurotoxin. There is ample evidence, however, that nonspecific damage can occur from 6-OHDA and can be of sufficient magnitude to produce observable behavioral effects (Butcher, Eastgate, & Hodge, 1974;Oltmans et al, 1977;Poirier, 1975). Variables that determine the amount of nonspecific damage include dose, concentration, and speed and size of infusion (Sotelo, Javoy, Agid, & Glowinski, 1973).…”

Section: Discussionmentioning

confidence: 99%

Differential effects on body weight of central 6-hydroxydopamine lesions in obese (ob/ob) and diabetes (db/db) mice.

Lorden¹

1979

Journal of Comparative and Physiological Psychology

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in Birmingham Obese (ob/ob) and diabetes (db/db) mice are genetic mutants that have been shown to have altered levels of central catecholamines as well as syndromes of obesity, hyperphagia, and hyperglycemia. Because the catecholamines, and particularly norepinephrine (NE), are implicated in the control of feeding, levels of central catecholamines were experimentally reduced in ob/ob and db/db mice to investigate the role of the catecholamines in these cases of spontaneously occurring obesity. Lesions produced by 6-hydroxydopamine (6-OHDA) were used to produce large depletions of NE and dopamine (DA) in both ob/ob and db/db mice and in lean control mice of the same background strains. In the db/db but not the ob/ob, central catecholamine depletion was accompanied by a significant and persistent weight loss and by a reduction in plasma glucose levels when compared with vehicle-infused controls. Treatment with the NE uptake blocker desmethylimipramine (DMI) prior to 6-QHDA infusions attenuated NE but not DA depletion. Diabetes mice that received DMI pretreatment showed a weight loss and decrease in plasma glucose proportional to the amount of NE depletion. Lean mice that received the 6-OHDA treatments showed only a transient weight loss and no significant change in blood glucose. It is concluded that abnormalities in central noradrenergic systems may account for part of the obesity syndrome observed in the diabetes mouse.Obese (ob) and diabetes (db) are two sin- Ingalls et al., 1950). Thermoregulatory degle gene mutations that cause obesity syn-fects, endocrinological abnormalities, and dromes in the mouse (Bray & York, 1971; changes in the activity of numerous enzymes Coleman, 1978; Hummel, Dickie, & Cole-are also characteristic of both syndromes (for man, 1966;Ingalls, Dickie, & Snell, 1950). reviews see Bray & York, 1971; Coleman, Although the mutant genes occur on differ-1978). ent chromosomes, the mutants are similar in Several lines of evidence suggest a central many respects (Coleman, 1978). Both are nervous system defect as a possible etiology autosomal recessive mutations, for example, for the ob and db syndromes. The hyperand in addition to obesity, both types of mice phagia and hyperinsulinemia of the mutants display hyperphagia, hyperglycemia, hy-are also typical of rats made obese by hypoperinsulinemia, and insulin resistance (Bray thalamic lesions (Steffens,

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Section: Discussionmentioning

confidence: 99%

Differential effects on body weight of central 6-hydroxydopamine lesions in obese (ob/ob) and diabetes (db/db) mice.

Lorden¹

1979

Journal of Comparative and Physiological Psychology

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“…The use of 6-OHDA was intended to provide an estimate of the contribution of NE depletion to subsequent changes in body weight. While most investigators agree that 6-OHDA has little or no effect on noncatecholaminergic neurons outside the immediate injection site (Breese & Traylor, 1970;Poirier, Langlier, Roberge, Butcher, & Kitsikis, 1972;Sotelo, Javoy, Agid, & Glowinski, 1973), it has also been argued that the toxic effects of 6-OHDA are the result of nonspecific damage (Butcher, Eastgate, & Hodge, 1974). In view of the controversy concerning the specificity of 6-OHDA, a group with electrolytic lesions was included in the present study to provide an estimate of the effects on body weight of unequivocal nonspecific damage at the lesion site.…”

Section: Methodsmentioning

confidence: 99%

Central noradrenergic neurons: Differential effects on body weight of electrolytic and 6-hydroxydopamine lesions in rats.

Lorden¹,

Oltmans²,

Margules³

1976

Journal of Comparative and Physiological Psychology

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“…Recent studies have demonstrated that in various arthropod neurons all of the major signaling functions of neuronsreception, conduction, and transmission-can survive for months after removal of the neuron soma and hence the cell's genetic apparatus (1)(2)(3). Thus arises the question of what functions are disrupted in such "somaless" neurons.…”

Section: Concen-mentioning

confidence: 99%

“…A major difficulty in the interpretation of behavioral and physiological changes caused by brain lesions is that the lesions produced by traditional methods [electric currents, radio frequencies, and transmitter-specific neurotoxins (1)] damage axons of passage as well as the cells and synapses within the area of the brain being studied (2).…”

mentioning

confidence: 99%

Axon-Sparing Brain Lesioning Technique: The Use of Monosodium-L-Glutamate and Other Amino Acids

Simson

Gold

Standish

et al. 1977

Science

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Infusions of monosodium-L-glutamate into the rostral hypothalamus, believed to contain neurons mediating satiety, produced persistent hyperphagia and obesity, thus suggesting that a brain lesion had been produced. Similar infusions into the caudal hypothalamus, believed to contain unmyelinated axons of passage that mediate satiety, failed to alter food intake or body weight. Histological examination of the affected tissue confirmed the behavioral evidence that suggests that this technique spares axons but destroys cell bodies. Infusion of several other amino acids also damaged neurons while sparing axons of passage.

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Evidence that punctate intracerebral administration of 6-hydroxydopamine fails to produce selective neuronal degeneration

Cited by 110 publications

References 39 publications

Differential effects on body weight of central 6-hydroxydopamine lesions in obese (ob/ob) and diabetes (db/db) mice.

Differential effects on body weight of central 6-hydroxydopamine lesions in obese (ob/ob) and diabetes (db/db) mice.

Central noradrenergic neurons: Differential effects on body weight of electrolytic and 6-hydroxydopamine lesions in rats.

Axon-Sparing Brain Lesioning Technique: The Use of Monosodium-L-Glutamate and Other Amino Acids

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