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Diverse effects of estradiol-17 beta: concurrent suppression of appetite, blood pressure and vascular reactivity in conscious, unrestrained animals.

Evidence from epidemiological and clinical investigations have suggested a relationship between estrogen-containing oral contraceptives and hypertension. The present series of studies, however, documents the ability of estradiol-17 beta, a natural ovarian estrogen, to lower resting blood pressure and pressor responses to norepinephrine in conscious, unrestrained guinea pigs. Arterial measurements were made of resting blood pressure and heart rate, plus pressor responses to intravenous infusions of 1.56 micrograms norepinephrine. Injection of 30 micrograms estradiol-17 beta reduced resting pressures up to 12% and pressor responses up to 20% in the interval from 12 to 48 hours postinjection. The estradiol treatment also significantly and reversibly lowered food intake, water intake, and body weight. These effects could be induced by either 3 or 30 micrograms of estradiol benzoate for up to 4 days if estradiol treatment was continued. Parallel studies indicated that NE-induced contractions of the isolated aorta were markedly reduced by pretreatment with estradiol. These studies indicate that natural ovarian estrogens may reduce blood pressure by reducing the contractility of the arterial smooth muscle.

Animals↗

Suppression of feeding and body weight by inescapable shock: modulation by quinine adulteration, stress reinstatement, and controllability.

Three experiments examined food intake and body weight in rats after exposure to one session of intermittent, inescapable electric shock. Quinine adulteration and shock both suppressed feeding (Experiment 1); recovery of feeding after shock was impeded when quinine adulteration was combined with a mild daily stress reinstatement (Experiment 2). Body weight also was suppressed by shock (Experiments 1 and 2); control over shock provided some protection against this deficit (Experiment 3). These results suggest roles for "finickiness" and vulnerability to mild stressors in the maintenance of eating disorders associated with stress and depression. The findings also may have implications for interpretation of deficits in appetitively motivated behaviors after stress.

Animals↗

Preference threshold for NaCl solutions and sodium homeostasis in hypophysectomized rats.

The NaCl preference threshold concentrations of male hypophysectomized (hypox) and intact rats were determined using a two-bottle choice paradigm. Although hypox rats ingested more total fluid daily (ml/100 g body weight), including water and NaCl solution, than intact rats, there were no significant differences between groups in either preference threshold (8.0 mEq/l) or preference maximum (90 mEq/l) concentrations. Further, the ratio of NaCl to total fluid ingested did not differ between hypox and intact groups throughout the large range of concentrations of NaCl solution presented to them. To assess their ability to conserve sodium, both intact and hypox rats were maintained on a sodium-deficient diet and distilled water for 3 days. Both groups reduced their urinary sodium outputs significantly compared to counterparts maintained on a sodium-replete diet. This suggests that the functional integrity of the renin-angiotensin-aldosterone system was maintained in the hypox rats. Resting plasma aldosterone concentrations, measured at the end of the experiment, did not differ significantly between groups. Assessment of completeness of hypophysectomy was made by measurement of daily urinary excretion of epinephrine and by change in body weight during the course of the experiment. Daily urinary excretion of epinephrine by hypox rats was reduced to one-tenth that of intact controls. Hypox rats also failed to grow during the course of the experiment. By application of both of these criteria, the rats were completely hypophysectomized.

Aldosterone↗

Effects of intracerebroventricular injection of dynorphin, leumorphin and alpha neo-endorphin on operant feeding in pigs.

Young pigs, which are useful experimental animals for biomedical research, were prepared with lateral intracerebroventricular (ICV) cannulae and housed individually in cages fitted with operant panels, with food and water ad lib. ICV injection of 200 micrograms of dynorphin A 1-17 or 1-13 resulted in a significant meal commencing within 2-5 min. Shorter fragments of dynorphin (1-10, 1-9, 1-8) were ineffective at inducing feeding as was dynorphin B (rimorphin). In the same situation, leumorphin and alpha neo-endorphin (200 micrograms) elicited significant feeding but beta neo-endorphin did not. Dynorphin 1-17 or 1-13, administered 5 min before feeding started, increased meal size when pigs were fed after 4-h deprivation. Naloxone ICV (0.4 mg) significantly reduced food intake in pigs feeding after 4-h deprivation and its main effect was in the second half of the meal. Naloxone also abolished the effect of ICV dynorphin. It is concluded that dynorphin and related endogenous opioids are involved in the regulation of food intake in pigs.

Animals↗

Reversal of a feeding-reward system by dexfenfluramine: neurochemical involvement.

In addition to its anorectic properties, dexfenfluramine may inhibit some manifestations of feeding-related reward. We attempted to verify this effect by measuring paw-lick latency on the hot plate test in rats conditioned to expect a palatable food. The involvement of variations in beta-endorphinergic, dopaminergic and serotonergic systems was assessed. Despite an inherent effect of increasing paw-lick latency, dexfenfluramine (1.5 mg/kg IP) partly reversed the expectancy-induced increase in this latency. Saline-treated "expectant" rats displayed elevated plasma beta-endorphin levels and reduced hypothalamic 5-HIAA/5-HT and DOPAC/DA ratios. Only the decrease in the DOPAC/DA ratio was reversed by dexfenfluramine, suggesting an involvement of the dopaminergic system in this dexfenfluramine-sensitive reward system.

Animals↗

Brain structures important for solving a sawdust-digging problem in the rat.

Young rats subjected to bilateral lesions to one of 37 different brain sites were initially trained to traverse a narrow runway to reach a goal box containing water. The test involved blocking a portion of the runway with sawdust and determining whether the animals would burrow through the sawdust to gain access to the goal box. Lesions to 30 brain sites produced deficient performance on the sawdust-digging problem. This study, combined with earlier investigation of 11 additional brain sites, shows that 41 of 48 total brain sites are involved in this task. These findings suggest that underlying brain mechanisms include a nonspecific mechanism and several specific mechanisms, such as visuospatial-attentional, visual discrimination, vestibular-proprioceptive-kinesthetic discrimination, response flexibility, but much less place learning mechanisms.

Animals↗

Lever-press conditioning in the crab.

An operant chamber has been developed for studying lever-press conditioning in the green crab Carcinus maenas. In one series of experiments, animals were presented with a single bar and were reinforced with food for every bar press. Performance increased over time and high rates of responding were observed after 2 days of training. The response rate was always higher than that for a yoked (noncontingent) control group. When the contingencies were switched, the animals adjusted to the new conditions. Discrimination in the lever-press apparatus was demonstrated in a second experiment in which crabs had to choose between two bars, one (S+) caused food to be dispensed while the other (S-) was inactive. Experimental animals pressed the S+ bar at a significantly higher rate than the S- bar. When the contingencies associated with the lever were reversed, animals learned to switch to the correct bar by the second day. It was not necessary to reinforce every response: animals maintained high rates of responding on a schedule where every other response was reinforced. Animals used different methods of pressing the bar; the most common was extension of the claw, predominantly at the meropodite-carpopodite joint.

Animals↗

Quality-specific differences in rat taste detection performance as a function of stimulus volume.

Taste detection performance for representatives of the four taste qualities as a function of stimulus volume (5 x 10(-4) to 1 x 1(-1) ml) was examined in rats using high-precision gustometry, computer-controlled operant procedures, nonparametric signal detection measures of sensitivity and responsivity, and blind control procedures. The overall sensitivity index was positively related to stimulus volume (rs = .60), with optimal detection performance attained with a 5 x 10(-3) ml stimulus volume for salty tastants and a 1 x 10(-2) ml stimulus volume for the other taste qualities. The overall responsivity index was inversely related to stimulus volume (rs = -.47), especially for sour and bitter tastants. These results are consistent with prior observations and demonstrate that operant methods using small tastant samples produce sensitive estimates of the rat's taste detection performance and response bias.

Animals↗

Discriminative properties of aversive electrical stimulations of the so-called "mesencephalic locomotor region": a parametric study.

The classical 2-lever food-reward-reinforced discrimination paradigm, although already successfully applied to study discriminative properties of positively reinforcing electrical brain stimulations (EBS), has not yet been used for negatively reinforcing (aversive) EBS. This study was aimed at assessing if such a discrimination paradigm could be used to demonstrate discriminative properties of aversive EBS of the so-called "mesencephalic locomotor region" (MLR). Fourteen rats were trained for food reward to press one lever in the presence of EBS of the MLR and the other lever in the absence of EBS. Discriminative control by EBS of the MLR was obtained in 11 rats, which were subsequently subjected to a parametric study. It was found that the discriminative properties of EBS of the MLR covaried with changes in the intensity, frequency and pulse duration of the EBS. Our data also suggest that the aversive dimension of the stimulation might constitute a component of the discriminative cue induced by these EBS.

Animals↗

Taste and olfactory modulation of feeding related neurons in behaving monkey.

Single neuron activity in the monkey lateral hypothalamus (LHA) was recorded by multibarreled electrode during a bar press feeding task. Activity of glucose-sensitive (GS) neurons decreased during bar press (BP) and reward (RW) periods. The inhibition was caused by activation of beta-adrenoceptors and opioid receptors respectively. Glucose-insensitive (GIS) neurons were excited during BP and RW, and at cue light (CL). Excitation at CL and BP was caused by activation of dopaminergic receptors. Among GS neurons, 66% responded to taste and 88% to odor. These responses were 39% and 52% in GIS neurons. GS neurons responded predominantly to two or more taste and odor stimuli while GIS neurons responded to only one stimulant. GS neurons have dense mutual connections with the prefrontal area, and GIS neurons are connected with the motor area. Gustatory and olfactory stimulation elicited responses in 67% of GS neurons and in only 21% of GIS neurons. Data suggest that GS and GIS neurons may have different functions in feeding: GS neurons process endogenous chemical information and integrated chemical sensations, and GIS neurons process external information processing, motor control and discriminative chemical sensations.

Animals↗

Amino acid imbalance, a nutritional model: serotonin3 mediation of aversive responses.

The feeding responses to essential dietary amino acid (AA) disproportion have been useful in nutritional studies. These responses involve first: recognition of the imbalance and second: rejection of the diet, likely via development of a learned aversion. In the rat, we have studied the role of the limiting AA and protein synthesis in the recognition phase by replacement of the limiting AA into a brain area essential for the initial depressed feeding response. We have also reported a reciprocal relationship between serotonin (5HT) activity and intake of imbalanced diets. High doses of the 5HT3 receptor antagonist, ICS 205-930 (ICS; 9 mg/kg IP), restored food intake to 85% or more of control intake. In the present experiments, similar treatment with ICS blocked the classical conditioned taste aversion to a saccharin solution paired with lithium chloride. These results suggest that the increased intake of AA imbalanced diets after ICS may be due to 5HT-mediated blockade of a learned aversion.

Amino Acids↗

Taste preference and protein nutrition and L-amino acid homeostasis in male Sprague-Dawley rats.

Changes in taste preference were investigated in a choice paradigm using rats under various states of protein nutrition. A preference for the umami taste substances, monosodium L-glutamate (MSG) with or without 5'-ribonucleotide (5'-guanosine monophosphate), was induced when dietary protein was within the normal range, but a preference for NaCl occurred under its marginal deficiency. A preference for both NaCl and glycine was induced under severe protein malnutrition, possibly reflecting the body's negative nitrogen balance. The strength of this preference paralleled the body's requirement for protein, and thus, like the protein requirement for normal growth, declined with age. When animals with L-lysine (Lys) deficiency consumed a Lys solution and began to grow normally, their intake of taste stimulus solutions changed from preferring NaCl and glycine to preferring MSG. The regulatory mechanism of preference for L-amino acid (AA) in rats deficient of an essential AA was related to the pattern of AA in plasma and brain. Data suggest that umami taste perception plays an important role in protein metabolism, and in maintenance of AA and ammonia homeostasis within normal limits.

Amino Acids↗

Effects of early postnatal gonadal steroids on extinction of a continuously food-rewarded running response.

In the present work the existence of sex differences (Experiment 1) on the acquisition and extinction of a continuously reinforced response in a short and narrow runway (100 x 9 x 10 cm) were investigated. In addition to the investigation of the basic sex differences in Experiment 1, the effect of postpuberal gonadectomy of male and female rats and the role of the early postnatal gonadal steroids on these situations were also examined in Experiments 2 and 3, respectively. In all experiments, no sex differences were found in acquisition. However, males extinguished faster than female rats. Gonadectomy of both sexes in adulthood, although it increases their latencies in acquisition, did not affect the differences between sexes during extinction. In contrast, in Experiment 3 female androgenization and male orchidectomy on day one after birth reversed the direction of sex differences found between control rats in the extinction period. Our findings suggests that the observed sex differences in extinction may be due to an underlying sexual dimorphism in the response inhibition process.

Androgens↗

Effect of chronic hypoxic treatment on the retention of fixed-interval responding.

The present experiments aimed to study the effects of hypoxic treatment (10 min on 3.5% oxygen) on the stabilized performance of rats in a fixed-interval schedule (FI 60 s). The hypoxic treatment was given once a day, for 3 days, immediately after the FI session. The results showed that the operant performance was disturbed from the very first posthypoxia FI session. There was a sharp drop in response rate, and changes in the temporal distribution of responses occurred. The data obtained greatly limit the importance of nonspecific factors in explaining these changes in performance. The results are discussed with reference to the retrieval hypothesis. In particular, it is suggested that the decreases of performance may be due to an effect of hypoxia on the retrieval mechanisms associated with long-term memory.

Animals↗

Effects of controllable vs. uncontrollable stress on circadian temperature rhythms.

The effects of sustained stress on body temperature were investigated in rats implanted with mini-transmitters that permitted remote measurement of body temperature. Temperature was first monitored during control conditions. Following the control period, rats were either shaped to avoid/escape signalled around-the-clock intermittent footshock (controllable stress) or yoked to the controlling rats such that the controlling rat and the yoked rat received shock of the same duration, but only the controlling rat could terminate shock by pulling a ceiling chain. Under control conditions, rats demonstrated regular rhythms in body temperature which averaged 1 degree higher during the 12-h dark cycle than the light cycle. Stress disrupted the rhythm and markedly decreased the night-day difference in temperature, especially in the yoked rats in which almost no difference between light and dark cycle temperature was seen. The disruption was most marked for the first days of stress. A regular temperature rhythm was reestablished following about 5 days of stress although the stress condition continued. Leverpressing for food was also affected by the stress conditions with both stress groups leverpressing less than controls and the uncontrollable stress group pressing less than the controllable stress group. These data offer additional evidence of the increased pathophysiological effects of uncontrollable as compared to controllable stress.

Animals↗

Stimulation in prefrontal cortex inhibits conditioned increase in blood pressure and avoidance bar pressing in rats.

In our previous work, it was established that stimulation in a precisely defined area of the prefrontal cortex and in nucleus accumbens inhibits motor and cardiovascular components of the defence reaction elicited by stimulation in hypothalamus or amygdala, but it did not inhibit operant appetitive bar pressing. In the present investigations it was shown that electrical stimulation in the same area of prefrontal cortex and in the nucleus accumbens inhibited blood pressure increases elicited by a conditioned sound. In another set of experiments it was also shown that it inhibited bar pressing developed with Sidman's schedule. It is therefore concluded that inhibition originating in the described region of the prefrontal cortex is specifically addressed to motor and cardiovascular components motivated by fear or aggression.

Animals↗

Sympathoadrenal effects on extinction of rewarded running in the rat.

Two groups of rats underwent adrenal demedullation or sham surgery before being trained to run in a straight runaway for food reward at a short intertrial interval (90 s). Half of each group of animals were then injected IP with the sympathetic neurotoxin, 6-hydroxydopamine HBr (6-OHDA; 30 mg/kg); the remainder received saline vehicle. After 3 more days of acquisition training, running was extinguished over 12 trials in all rats. Running times were similar in all groups at the start of extinction. In saline-injected animals, extinction proceeded more slowly in the demedullated than in the sham-operated group, but this effect was largely abolished by 6-OHDA. Consistent with previous results, there was evidence that 6-OHDA facilitated extinction, irrespective of adrenal demedullation, but this effect was most apparent in the time taken to emerge from the start-box. The rats were killed two days after the end of the experiment; cardiac noradrenaline levels were depleted by 83% of control values in 6-OHDA-treated animals. The results suggest that the adrenal medulla and sympathetic neurones have opposing and interacting effects on the response to nonreward.

Adrenal Glands↗

Sucrose to polycose preference shifts in rats: the role of taste, osmolality and the fructose moiety.

Rats given continuous access to 32% sucrose and Polycose solutions initially preferred sucrose but over days reversed their preference and drank more Polycose than sucrose. The role of taste and postingestive factors in this preference shift were investigated in several experiments. A strong and persistent preference for saccharin-sweetened Polycose over unsweetened Polycose was eliminated by intervening experience with a sucrose vs. Polycose choice test, suggesting that the postingestive effects modify the attractiveness of sweet taste. Osmolality differences between sucrose and Polycose were ruled out as an important factor; increasing the osmolality of Polycose by addition of glucose did not prevent the sucrose to Polycose preference shift. Rather, the shift in preference appears to result from some postingestive consequence of the fructose moiety contained in sucrose. This is indicated by the findings that rats did not reliably prefer a fructose-Polycose mixture to a sucrose solution in long-term tests, but developed preferences for maltose over sucrose solutions, and for glucose + Polycose over fructose + Polycose mixtures. Also, a 32% glucose solution was strongly preferred to a 32% fructose solution. Other studies examined the parameters of the sucrose to Polycose preference shift. The Polycose preference was accomplished by increases in both Polycose meal size and frequency. It occurred only with relatively concentrated solutions (16 and 32%) and was incomplete when the carbohydrates were presented in powdered form. Preexposure to Polycose enhanced the preference shift, whereas preexposure to sucrose retarded the development of the preference, suggesting that the shift occurs because Polycose is more rewarding, rather than because sucrose is more aversive. Polycose preference was lost after several days without the solutions but redeveloped in subsequent sucrose vs. Polycose choice tests. Thus the preference shift appears to be due to taste-postingestive consequence conditioning but its expression is dependent upon the nutritional state of the animal.

Animals↗