LH syndrome and brain catecholamine levels after lesions of the nigrostriatal bundle

Lesions of the nigrostriatal bundle (NSB), whose fibers pass through the medial portions of the internal capsule and the immediately adjacent lateral hypothalamus (LH), produced a more severe aphagia, adipsia, and disturbance of water regulation than did lesions of the medial forebrain bundle (MFB). When deprived of food, animals with NSB lesions drank significantly less than controls and animals with MFB lesions. NSB lesions also produced greater decreases in telencephalic content of the catecholamines than MFB lesions, while the reverse was true for serotonin. Water intake during food deprivation was highly correlated with telencephalic catecholamine levels in animals with NSB lesions. Thus, the inability to regulate water intake in the absence of food, one of the characteristic and long lasting effects of the LH syndrome, appears to be due to destruction of the NSB and the consequent decline in telencephalic content of catecholamines.     

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

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.     

Subfornical organ participates in salt appetite

The effects of subfornical organ (SFO) lesions on salt and water intakes after sodium depletion were studied. Water and salt intakes were measured over 45 hr during a regimen that combined furosemide diuresis and access to low-sodium diet. Water was solely available for 23 hr after diuresis, and water and 0.3 M NaCl solution were available in choice for the next 22 hr. After diuresis, rats with SFO lesions drank significantly less water in 2 hr than controls but achieved equivalent water and sodium balances before salt access 20 hr later. After salt access, rats with SFO lesions drank significantly less saline and water in 2 hr than controls but had similar saline and water intakes over the next 20 hr. Thus, SFO lesions blunted acutely, but not chronically, saline and water intakes to sodium depletion, and the blunted intakes are not explainable by hydrational status.     

Competitive behavior: intact male rats but not hyperdefensive males with medial hypothalamic lesions share water with females

Male hooded rats with medial hypothalamic lesions or sham lesions were given tests of defensiveness toward an experimenter. The 8 lesioned males with the highest defensiveness scores and 7 sham-lesioned males were each placed in a double cage with a single intact female. For each pair of rats, food was continuously present but water was available for only 1 hr/day through a single water spout. Beginning on the fifth day of water deprivation, each pair of animals was given a 4-min water competition test on 3 consecutive days. Competition for water was created by placing a plastic ring over the hole in the cage where the water spout entered the cage. The ring restricted access to the spout to a single animal and was put in place 5 min before water was given. One hr following the competition test, each pair of animals was given access to a single unencumbered spout for a 1-hr period. Rats with medial hypothalamic lesions drank significantly more and initiated more aggression than their female cagemates during the 4-min competition tests. Sham-lesioned rats neither drank significantly more nor were more aggressive than their female cagemates. These results are consistent with previous observations indicating that the aggressiveness of rats with medial hypothalamic lesions can be elicited by a competition situation.     

Relationship of dietary fat content to food preferences in young rats

Weanling rats were fed either a high-fat (30% of calories) or a low-fat (10% of calories) diet for four weeks, after which fat preference was assessed using a choice paradigm. Fat preference was measured during 2-hour intake tests in which three peanut butter/peanut oil mixtures containing 0.50, 0.61, and 0.71 grams fat/gram were offered to each animal. Rats fed the high-fat (HF) diet preferred the highest-fat mixture and consumed more total fat during intake tests than animals fed the low-fat (LF) diet. Intake of NaCl and sucrose solutions was measured during separate intake tests. LF-fed rats drank more NaCl solution than HF-fed rats. Following these tests a subgroup of the LF-fed animals was fed the HF diet, and a subgroup of the HF-fed group was fed the LF diet for a further four weeks. Upon repetition of the intake tests, rats that had been fed the HF diet during the initial four weeks still preferred the highest-fat mixture.     

Naloxone modifies sugar-water intake in rats drinking with open gastric fistulas

The effects of the opiate antagonist naloxone (NX) on fluid preference and intake were determined in rats drinking with chronically indwelling gastric fistulas. The subjects were tested both after 22.5 hr fluid deprivation, and no deprivation, with open fistulas (sham drinking), as well as with closed fistulas. Following an injection of either saline or NX (0.5–10.0 mg/kg, administered SC), or no injection, the subjects were given the choice to drink water or 10% sucrose, in a two-bottle test, for 1 hr/day. With open fistulas, and following fluid deprivation, the animals sham drank both sucrose and water, but had a strong preference for sucrose. When not fluid deprived, the same animals sham drank sucrose almost exclusively. NX significantly reduced sucrose intake by the sham drinking animals, in both the deprived and not deprived conditions, but did not modify fluid preference. These data support the idea that NX modifies affective reactivity to palatable solutions, and that NX's antidipsogenic actions are not due to feedback from post-absorptional events.     

Habenula lesions alter synaptic plasticity within the fimbria-accumbens pathway in the rat

Both the habenula and the nucleus accumbens, and especially the glutamatergic innervation of the latter from the hippocampus, have been hypothesized to be involved, in different ways, in the pathophysiology of cognitive disturbances in schizophrenia. Lesions of the habenula produce disturbances of memory and attention in experimental animals. As the habenular nuclei have been shown to influence the release of many neurotransmitters, both in the hippocampus and the nucleus accumbens, we examined in this study the effects of bilateral habenula lesions on the plasticity of the fimbria-nucleus accumbens pathway, by means of the long-term depression phenomenon in freely moving rats. Long-term depression, induced within the shell region of the nucleus accumbens by low-frequency stimulation of the fimbria, was exaggerated and showed greater persistence in habenula-lesioned rats compared with sham-operated animals. These results indicate that plasticity in the fimbria-nucleus accumbens pathway is altered by habenula lesions in a way similar to previously-reported effects of stress and the psychosis-provoking agent ketamine. Moreover, they strengthen the views that the habenula belongs to systems, mediating higher cognitive functions, which involve the hippocampus and the nucleus accumbens. Finally, this study suggests that dysfunction of the habenula could contribute to cognitive alterations in diseases such as schizophrenia, where the habenula is reported to exhibit exaggerated calcification.     

Diurnal patterns of food intake and plasma corticosterone levels in lactating rats

The diurnal patterns of food intake and plasma corticosterone levels were determined in lactating Wistar-Imamichi rats maintained in a light (14 L: 10 D, lights on 0500 hr) and temperature (24±2°C) controlled animal room. Lactating mothers with four or more than eight pups showed a characteristic diurnal pattern of food intake with high rates of intake around the time of lights off. The diurnal rhythmicity of food intake seemed to disappear in late lactation in mothers with more than eight pups. The plasma corticosterone concentration on day 9 of lactation displayed a diurnal rhythm with high values at 1700 hr and 2100 hr. The rhythmicity of the corticosterone levels was abolished on day 16 of lactation and a high level was maintained throughout a 24 hr period. Since the diurnal rhythm of the corticosterone level was shifted in animals fed during the restricted period (0900–1700 hr) from days 2 to 9 of lactation, the appearance of diurnal rhythm of corticoid secretion seemed to depend on the diurnal feeding rhythm in lactation as well as in the estrous cycle.     

Regulation of feeding behavior in the prepubertal female rat.

Responses to challenges of long-term regulation of feeding behavior were compared between adult and weanling female rats. Adulteration of a high fat diet with NaCl caused both adult and weanling rats to reduce their food intake, but neither group refused to eat. Food deprivation for 24 hr was followed by an increase in feeding for both adult and weanling animals during a period when food intake is normally very low. Continued limited food access to 2 hr during the light period was compensated for by an increase in the normal food intake for this period for both adult and young female rats. It was observed that both adult and weanling rats showed a marked preference for the more dilute glucose solution when given a choice. In addition, both groups maintained a constant caloric intake during presentation of the glucose solutions by adjusting their intake of a solid food source. In each challenge of long-term regulation of feeding behavior, the response of weanling animals was as good or superior to that shown by adults. It is concluded that weanling female rats regulate their feeding just as adults to maintain long-term energy balance. It was also observed that bilateral lesions placed in the ventromedial hypothalamus (VMH) at 21 days of age resulted in reduced daily food intake and retarded body weight gain. Furthermore, young rats with VMH lesions failed to respond to 24 hr of food deprivation or limited food access. These data suggest an important role for the VMH in the long-term regulation of feeding in young rats.     

Growth hormone secretion and ultradian rhythms in growth-retarded rats with dorsomedial hypothalamic lesions

Rats with lesions of the dorsomedial nucleus of the hypothalamus (DMN-L) are hypophagic and have reduced linear growth and body weight, but normal body composition. Male Sprague-Dawley rats (170-190 g) housed individually under a 12:12 L:D schedule with lights out at 1430 hr received jugular cannulas, and on return to precannulation body weight (4.2 +/- 0.6 days), they received bilateral electrolytic DMN-L or sham-operations (SHAM). Rats with DMN-L (n = 8) were hypophagic postsurgery and weight less (p less than 0.05) than SHAM at six days postlesion surgery. The difference in body weight between the two groups continued to expand over the next four weeks. Six days postsurgery, the rats were bled (RBC's returned in 10% BSA-saline) every 15 minutes between 0600-1215 hr and growth hormone (GH) subsequently assayed. The total GH secretion, as computed from the area under each rat's ultradian pattern, was similar in both groups (DMN-L versus SHAM, 2952.2 +/- 346.5 versus 2950.4 +/- 337.5). Using the PULSAR computer program, the baseline secretion (12.2 +/- 4.0 versus 11.8 +/- 2.7 ng/ml), total number of peaks (2.4 +/- 0.4 versus 2.4 +/- 0.2), and interpeak interval (2.8 +/- 0.5 versus 2.7 +/- 0.4, hr) were not significantly different between the DMN-L and SHAM rats, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Water intoxication death following hypothalamic lesions in the rat.

Rats received large, bilateral lesions of the ventromedial hypothalamus. Water or saline intakes, urine outputs and body temperatures were observed for up to 24 hr after surgery. Fifty percent of the operated animals drank excessively and died within 4-6 hr when permitted access to water. Urine outputs were low and symptoms of water intoxication were evident. When allowed access to saline, outputs rose and the number of animals which survived increased as the saline concentration increased. Body temperatures approached 40 degrees C during drinking, but did not differ from operated animals which refused to drink. It was concluded that the deposition of metallic ions strongly stimulates a hypothalamic drinking system which results in overhydration and water intoxication death.     

Interaction between the septal area and the subfornical organ in the control of water intake induced by thirst-eliciting procedures

Rats bearing lesions in the septal area followed by lesions in the subfornical organ were submitted to various thirst-eliciting procedures. The rats with hyperdipsia induced by lesions of the septal area drank more water than either during the control period or after lesion of the subfornical organ under the same thirst-eliciting or angiotensin-liberating stimuli (polyethyleneglycol, isoproterenol, water deprivation and ligation of the inferior vena cava). The overdrinking elicited by lesions in the septal area was blocked after lesion of the subfornical organ. Neither hypovolemia, nor hypotension or water deprivation could elicit increased water intake in animals whose subfornical organ had been destroyed. Animals with lesions in the subfornical organ showed decreased water intake after cellular dehydration. The results obtained suggest that the subfornical organ acts as a more important structure than the septal area in the regulation of water intake elicited by angiotensin, with two opposite effects: a direct one facilitating water intake, and an indirect one inhibiting the septal area. The septal area has an inhibitory effect on the subfornical organ and on water intake.     

Adolescent social stress and social context influence the intake of ethanol and sucrose in male rats soon and long after the stress exposures

Social instability stress in adolescent rats (SS; postnatal day 30–45, daily 1 hr isolation +new cage partner) alters behavioural responses to psychostimulants, but differences in voluntary consumption of natural and drug rewards are unknown. SS also is associated with an atypical behavioural repertoire, for example reduced social interactions. Here, we investigated whether SS rats differ from control (CTL) rats in ethanol (EtOH) or sucrose intake in experiments involving different social contexts: alone, in the presence of an unfamiliar peer, in the presence of its cage partner, or in competition against its cage partner. SS rats drank more EtOH than CTL rats irrespective of social context, although the effects were driven primarily by those tested soon after the test procedure rather than weeks later in adulthood. SS and CTL rats did not differ in sucrose intake, except in adulthood under conditions of competition for limited access (SS>CTL). Adolescent rats drank more sucrose than adults, in keeping with evidence that adolescents are more sensitive to natural rewards than adult animals. Overall, adolescent SS modified the reward value of EtOH and sucrose, perhaps through stress/glucocorticoids modifying the development of the mesocorticolimbic system.     

Drinking to intracellular dehydration following vagotomy in rats

Abdominally vagotomized rats maintained on a solid diet drank less and had longer latencies to drink than sham vagotomized rats following IP injection of an osmotic load (0.75 M NaCl, 1% BW). However, these two groups did not differ in latency or water intake following injection of isotonic saline. Since both vagotomized and control rats drank more water and had shorter latencies following injection of hypertonic saline than after isotonic saline, vagotomy apparently attenuated but did not abolish osmotic drinking. Maintenance on a liquid diet and a brief fast prior to testing (to ensure an empty stomach) did not alter these results, indicating that the impairment of gastric emptying of solid food that accompanies total abdominal vagotomy cannot account for the attenuation of osmotically induced drinking. Furthermore, this deficit was seen even when intracellular dehydration was produced at different times during the circadian cycle and when water presentation was delayed 0.5 hr postinjection. In addition, vagotomized rats drank less than control rats following 16-hr water deprivation and exhibited a lower water-food ratio on ad lib regimen. However, vagotomized and sham vagotomized rats exhibited the same relative day-night difference in water consumption as well as short latency response to thermal pain, which with other results indicates that vagotomy did not result in a general impairment of behavior. These findings suggest that osmotic perturbations are detected by the viscera and the information conveyed to the brain via afferent vagus nerves.     

Diet selection following area postrema/nucleus of the solitary tract lesions

Ten adult Long-Evans male rats were offered access to fat, protein and carbohydrate from separate sources. After adaptation to this diet, 5 animals received thermal lesions of the area postrema and adjacent caudal-medial portion of the nucleus of the solitary tract (AP/cmNTS). The remainder were sham-operated. AP/cmNTS lesioned rats ate significantly less and lost more weight than controls during the first postsurgery measurement period (Days 4–13 after lesioning). The decrease of food intake of AP/cmNTS lesioned rats was due to reduced fat consumption. Carbohydrate and protein intakes of lesioned animals did not differ from those of controls. Food intakes and weight changes of lesioned rats did not differ from those of controls during days 14–23 after lesioning. Intake of fat by lesioned animals remained low but was no longer significantly different from that of controls. Carbohydrate and protein intakes of lesioned rats increased slightly but did not differ significantly from those of nonlesioned controls.     

Excessive drinking by rats with septal lesions during hypovolemia induced by subcutaneous colloid treatment

Rats with septal lesions consumed much more water than control rats did during a 24-hr test after subcutaneous administration of polyethylene glycol solution. Previous experiments have demonstrated that plasma renin activities are 35 to 70 times greater than basal levels after this treatment, and that rats with septal lesions overdrink when comparable levels are produced by systemic administration of renin. Thus, it seems likely that angiotensin was largely responsible for the exaggerated intakes that were elicited by the colloid. However, given their special sensitivity to the thirst-inducing effects of angiotensin, it is noteworthy that the brain-damaged animals drank normally during the first 8 hr of the test period because by then plasma renin activities should have been increased to values 20 to 40 times greater than basal levels. These findings therefore suggest that angiotensin usually contributes little as a dipsogen to thirst, even during such extensive hyperreninemia, and that it is only when angiotensin levels are higher still that drinking is stimulated.     

Effects of small basolateral amygdala lesions on ingestion in the rat

Using a variety of tests, the effects of small bilateral electrolytic lesions restricted to either anterior (BLa) (n=8) or posterior basolateral (BLp) (n=8) nucleus of the amygdala on food and fluid ingestion were measured. BLa lesions increased latency to eat in a novel environment, relative to sham operated controls (n=9). Neither lesion affected intake of 0.1% HCl, either on first exposure or after pairing with IP LiCl (conditioned taste aversion). However, water intake of both lesion groups was higher than normal during limited access water deprivation. Ad lib food and water intake were normal in both groups, but BLa animals drank more water than shams in response to acute cellular dehydration (IP 2M NaCl). Ad lib 24 hour intake of a range of concentrations of sucrose (0.02 M, 0.2 M, 2 M) and NaCl (0.05 M, 0.2 M, 1 M) was normal in BLp animals, but the BLa group drank less of the normally most preferred concentration of NaCl (0.2 M) than shams. The BLa group did not increase food intake significantly after insulin administration. These lesion induced alterations are discussed in relation to previous studies on damage to basolateral amygdala, and possible anatomical substrates for the effects are briefly discussed.     

Water handling by the sabra hypertension prone (SBH) and resistant (SBN) rats

The renal handling of water by SBH and SBN rats was evaluated under basal conditions and following various intervention procedures. During 17 weeks of unrestricted water intake, SBH rats drank less water and excreted less urine with a higher osmolality than SBN. The differences in urine volume and osmolality persisted during 2 weeks of paired water intake. Acute water loading elicited comparable dilution of the urine in the two strains. Water deprivation for 48 h resulted in a marked rise in urine osmolality, which tended to be higher in SBN. Administration of exogenous vasopressin in water loaded animals caused a similar rise in urine osmolality. Papillary solute and urea content was higher in SBH than in SBN, but comparable in water loaded animals. The results show that although SBH differ from SBN rats in the handling of water under basal conditions, their renal diluting and concentrating capacity is comparable at extreme conditions. GFR and RBF were equal in both strains. The data suggest that SBH rats have increased renal water reabsorption as compared to SBN, which may be mediated by ADH, PG or other mechanisms. This characteristic may be related to their propensity to develop hypertension.     

Naloxone suppression of food and water intake and cholecystokinin reduction of feeding is attenuated in weanling rats with dorsomedial hypothalamic lesions

In Experiment 1, sham operated (SCON) and dorsomedial hypothalamic nuclei (DMN) lesioned (L) rats were given saline or naloxone (0.1, 1.0 or 2.0 mg/kg) just prior to the onset of the dark cycle, lights out. Compared to saline injections, naloxone at all doses suppressed the cumulative food intake of the SCON during the second and third hr of measurement. Naloxone was without significant effect on the food intake of DMNL rats. Similar results were obtained in Experiment 2, except that naloxone at 2.0 mg/kg significantly suppressed the DMNL rats' food intake by the fourth hr of measurement. Cumulative water intake of both groups was significantly suppressed by naloxone in both experiments but its effects appeared to be attenuated in the DMNL group. In a preliminary trial cholecystokinin octapeptide (3.0 and 6.0 micrograms/kg) given at the onset of the dark cycle significantly suppressed the food intake of the SCON group but had no significant effect on the DMNL rats. The possibility exists that the reduced food intake and lower body weight of DMNL rats may partially result from damage to an opioid system. The data also tentatively suggest that DMN may play a role in cholecystokinin-induced satiety.     

Dorsal hippocampus, CA3, and CA1 lesions disrupt temporal sequence completion

An experiment was designed to evaluate effects of dorsal hippocampus, dorsal CA3a,b, dorsal CA1, and control lesions on performance of a temporal sequence task. Rats were trained on a sequential learning task involving six spatial locations on a radial 8-arm maze. After initial training followed by surgery, it was found that all lesioned animals were able to remember the sequence. To test temporal sequence completion, rats were started at different positions in the sequence and expected to complete the remainder of the sequence. The results indicate that control rats had no difficulty completing the sequence, regardless of starting point. In contrast, rats with dorsal hippocampus and dorsal CA3a,b lesions made errors by always returning to the first position in the sequence, regardless of which start position was used, whereas rats with dorsal CA1 lesions made random errors in the process of completing the sequence and did not appear to remember the serial order of the spatial sequence. This suggests that the dorsal hippocampus, and specifically the dorsal CA3 in conjunction with CA1, may be involved in temporal pattern completion processes.