Lore Grossman

Iontophoretic injections of kainic acid into the rat lateral hypothalamus: Effects on ingestive behavior

Iontophoretic injections of kainic acid into the dorsolateral hypothalamus of rats resulted in localized, partial depletions of neurons from the area without significant damage to adjacent areas of the diencephalon, including the zona incerta, dorsomedial hypothalamus and anterior as well as posterior regions of the hypothalamus that have been reported to be severely affected by mechanical injections of KA into the LH. Distant KA-sensitive structures such as the hippocampus and temporal lobe also showed no discernible neuronal loss or glial proliferation. The neuronal loss within the LH was far less severe after iontophoretic injections than after mechanical injections of KA. Our KA treated animals nonetheless displayed transient aphagia and adipsia, followed by variable periods of hypophagia and hypodipsia. After recovery of essentially normal ad lib feeding, the KA-treated rats failed to eat in response to a glucoprivic challenge (2-deoxy-D-glucose) but consumed normal quantities of water during periods of food deprivation. Their drinking response to hypertonic saline was somewhat reduced during the first hour after the treatment but normal at 6 as well as 24 hours. Unilateral KA injections produced only transient changes in ad lib food intake.

Surgical interruption of the anterior or posterior connections of the hypothalamus: Effects on aggressive and avoidance behavior

Abstract Transverse surgical cuts through the anterior hypothalamus, just anterior to the level of the ventromedial nuclei, which interrupted most, if not all of the anterior projections to and from the hypothalamus, inhibited intraspecies aggressive behavior in female rats but produced little or no change in shuttle box avoidance behavior. Transverse surgical cuts through the posterior hypothalamus, just posterior to the level of the ventromedial nuclei, which interrupted all posterior connections of the hypothalamus except those coursing the formix or the ventrolateral hypothalamus, markedly depressed shuttle box avoidance behavior but affected aggressive reactions little or not at all. Both types of cuts produced hyperphagia and hyperdipsia but these effects had subsided in most animals before the tests of avoidance and aggressive behavior were begun. Tests of motor coordination and catatonia indicated that the observed behavioral deficits could not be due to a general motor impairment. The implications of these results are discussed with reference to previously reported effects of parasagittal cuts which transect the lateral connections of the hypothalamus.

Food and water intake in rats after transections of fibers en passage in the tegmentum.

Abstract A 145 micron diameter wire knife was used to transect fibers en passage in ventral, medial, and dorsal aspects of the tegmentum. Data from 74 rats with bilaterally symmetric cuts indicate that the interruption of fibers which course through the central region of the tegmentum result in hyperdipsia. Three distinct syndromes were observed: (a) extreme hyperdipsia beginning on the first or second day after surgery and persisting for 4–6 days; (b) a smaller increase in water intake beginning on the first or second day after surgery and persisting for the duration of the experiment; and (c) normal or subnormal water intake for several days after surgery followed by a sharp increase which persisted for 4–6 days. Cuts through the dorsolateral tegmentum consistently produced hyperphagia in male rats maintained on a dry pellet diet. The magnitude of the effects was comparable to that seen in male rats after ventromedial hypothalamic (VMH) lesions. These cuts, as well as others which did not result in hyperphagia, abolished the normal feeding responses to 2-deoxy-D-glucose (2-DG) without affecting the feeding response to insulin. Some of our cuts produced significant overeating but no commensurate weight gain, suggesting that metabolic disturbances may have occurred. Knife cuts of comparable size through the ventral third of the tegmentum, the pons, or the ventral aspects of the central grey, failed to affect either food or water intake reliably. Histological evidence of minimal direct damage to cellular components of the region of the behaviorally effective cuts and their extensive rostro-caudal distribution indicate that direct damage to perikarya of tegmental neurons probably is not responsible for the effects of the cuts.

Parametric study of the regulatory capabilities of rats with rostromedial zona incerta lesions: Responsiveness to hypertonic saline and polyethylene glycol☆

Abstract Rats with lesions in the dorsomedial zona incerta (ZI): (1) were hypodipsic; (2) drank little or nothing during periods of food deprivation; (3) drank little or nothing after injections of 5 ml of 0.50 M, 0.75 M, 1.0 M or 2.0 M NaCl solutions (some animals displayed delayed responses to the highest dose, 6 and 24 hr after the injection); (4) drank normal quantities of water or saline after 5 ml of 15%, 20%, or 30% PG (half of the animals that had shown absent or severely impaired responses to hypertonic saline; the other half did not drink saline or water in response to any dose of PG except the highest—5 ml of 30%); (5) sharply reduced or abolished sodium appetite; (6) reduced or abolished the feeding response to 2-DG without affecting ad lib food intake. Similar effects on 2-DG eating and sodium appetite (but not on water intake under ad lib or food-deprivation conditions, or on drinking in response to hypertonic saline or PG) were produced by lesions in ventral thalamus or dorsomedial hypothalamus.

Effects on hypothalamic and telencephalic NE and 5-HT of tegmental knife cuts that produce hyperphagia or hyperdipsia in the rat☆

Knife cuts in the coronal plane through various aspects of the midbrain tegmentum produced hyperphagia, hyperdipsia, or no effect on ingestive behavior. All of the cuts significantly depleted NE and 5-HT from hypothalamus and forebrain. The brains of hyperphagic or hyperdipsic animals did not differ from those of normophagic and normodipsic animals with respect to hypothalamic NE or 5-HT or telencephalic NE. Both hyperphagic and hyperdipsic animals had significantly lower concentrations of 5-HT in forebrain than rats which sustained similar cuts in the tegmentum which did not affect ingestive behavior.

Zona incerta lesions: regulatory drinking deficits to intravenous NaCl, angiotensin, but not to salt in the food.

Abstract Rats with bilateral damage to the anterior zona incerta (ZI) showed small and delayed drinking responses after IP hypertonic NaCl injection, but they normally excreted most of the salt load within 6 hr. The impaired drinking responses were also evident after nonpainful intravenous (IV) NaCl infusions. After nephrectomy, rats with complete ZI lesions did not drink within 24 hr of the NaCl infusion. Rats with less complete lesions showed reduced and delayed drinking. In contrast to these profound osmoregulatory drinking impairments, all of the lesioned rats increased their water to food ratio when fed a 3% NaCl-supplemented diet. ZI lesioned rats did not drink in response to IV infusions of angiotensin II. The role of the ZI in drinking behavior is discussed in terms of the paradigm-dependent nature of these results, and parallels with other findings are considered.

Impaired feeding responses to intragastric, intraperitoneal, and subcutaneous injections of 2-deoxy-D-glucose in rats with zona incerta lesions.

Abstract Rats with rostromedial zona incerta lesions displayed severely attenuated feeding responses to intragastric injections of 750, 1000, or 1250 mg/kg of 2-deoxy-D-glucose (2-DG) which elicited optimal feeding and few debilitating side effects in neurologically intact controls. Rats with ZI lesions also ate little, if at all, in response to low doses (200 and 300 mg/kg) of 2-DG administered subcutaneously which were approximately as effective in controls as the intragastric injections of much larger doses. The experimental animals also responded poorly to a standard (600 mg/kg) intraperitoneal (IP) injection of 2-DG but showed only a small impairment in responding to 8 Units/kg of insulin. These results suggest that less stressful routes of administration do not ameliorate the ZI rats severe deficit in responding to 2-DG that has been reported after IP injections of large doses of the compound, and replicate the observation that insulin feeding is impaired relatively little if at all.

Some biochemical effects of zona incerta lesions that interfere with the regulation of water intake

The concentration of NE, DA and 5-HT in forebrain, striatum, and hypothalamus was measured after zona incerta (ZI) lesions that have been shown to result in general hypodipsia; adipsia during periods of food deprivation; impaired or abolished drinking in response to osmotic challenges (but not polyethylene glycol); impaired drinking after systemic isoproterenol or central angiotensin; and impaired or abolished feeding in response to 2-deoxy-D-glucose. The lesions produced a significant (40-50%) depletion of forebrain NE but a correlational analysis of the behavioral and biochemical effects of the lesions failed to indicate a causal relationship. The lesions did not reliably affect (a) forebrain DA or 5-HT; (b) striatal DA or 5-HT; (c) hypothalamic DA, NE or 5-HT. The results of these experiments indicate that significant impairments in ingestive behavior can be demonstrated in animals with diencephalic lesions that do not result in striatal (or forebrain) DA depletions. This confirms previous behavioral analyses showing that ZI lesions which interfere with ingestive behavior do not produce the debilitating sensory or motor dysfunctions typical of the rat with lateral hypothalamic lesions.