Increased motivation in rats with ventromedial hypothalamic lesions.

25 female albino rats were implanted with chronic electrodes aimed for the ventromedial hypothalamic area (VMH), deprived to 82% of normal weight, and trained on a 2-min VI schedule for food reinforcement. After rates of response became stable, bilateral DC lesions were made, and weight was held constant. Over 10 days after lesioning, Ss with extensive VMH damage showed increases in rates of response for food. Unilateral lateral hypothalamic lesions resulted in decreases in response rates followed by recovery, regardless of VMH damage. Under more severe deprivation (48 hrs and 72 hrs), Ss with extensive VMH damage showed further increases in response rate. Results indicate that VMH lesions increased food motivation. Some factors which can produce opposite results are discussed. (38 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Continuing gonadal function in rats with ventromedial hypothalamic area lesions.

Gonads of 24 female and 20 male rats with ventromedial hypothalamic (VMH) or sham lesions were examined after 67 days in constant light. Results show that VMH- and sham-lesioned males had normal testes. Sham-lesioned females had small ovaries and no corpora lutea (CL). 7 VMH females had larger ovaries with CL and numerous follicles, 4 had larger ovaries with no CL but numerous follicles, and 4 had ovaries resembling those of sham-lesioned females. Damage was confined to the VMH in females with CL, but it included less or more of the anterior hypothalamus in females lacking CL. Results suggest that since VMH damage permits estrous cycling to continue, the intact VMH acts to inhibit cycling in constant light. (30 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Conditioned taste aversion in lean and obese rats with ventromedial hypothalamic knife cuts.

Assessed the development of a conditioned taste aversion (CTA) in 60 female Sprague-Dawley rats made hyperphagic with parasagittal knife cuts in the ventromedial hypothalamus (VMH). Ss were water deprived and presented with a .1% saccharin solution paired with injections of either LiCl or NaCl. In Exp I, VMH Ss tested at a nonobese weight level did not differ from sham-operated controls in acquisition and extinction of the CTA. In Exp II, moderately obese VMH Ss displayed a stronger CTA than did sham-operated controls as evidenced by slower extinction. A 2nd group of obese VMH Ss given an amount of LiCl equivalent to that given to the controls also displayed retarded extinction of the CTA. Results reflect an obesity-induced suppression in appetitive motivation. (29 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Hyperinsulinemia in rats with ventromedial hypothalamic lesions: Role of hyperphagia.

Examined the relation of hyperinsulinemia to hyperphagia in 18 female hooded Long-Evans rats with lesions of the ventromedial hypothalamus (VMH). Plasma insulin and glucose levels were assayed after a 4-hr fast and 17 min after the initiation of a meal (6 ml of sweetened milk in 7 min) in 8 other Ss with sham lesions, VMH Ss maintained at preoperative body weight by food restriction, and VMH Ss fed ad lib. Both VMH groups displayed basal and postabsorptive hyperinsulinemia compared with the sham-operated group, but insulin levels were greatest under the ad lib feeding condition. It is suggested that VMH hyperinsulinemia is due both to a primary effect of the lesion and to hyperphagia and that marked obesity can result in the absence of basal hyperinsulinemia as a result of hyperphagia with consequent postabsorptive hyperinsulinemia. (14 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of ventromedial hypothalamic lesions on hunger-motivated behavior in rats.

Previous studies show that lesions of the ventromedial hypothalamus (VMH) paradoxically increase food intake and decrease hunger motivation in the rat. In a series of experiments designed to examine this paradox, independent groups of VMH-lesioned, female hooded rats (N = 48) were tested on a VI schedule or were run in a straight alley to a food reward. Rate of food ingestion was also measured for all Ss. Performance of the VMH and control groups was compared at identical deprivation conditions defined in terms of preoperative base-line weights (80, 90, 100, and 110%). All test measures showed a significantly higher level of performance for VMH-lesioned Ss at the least severe deprivation conditions. Results suggest that the previously reported VMH paradox originated, in part, from inappropriate testing procedures and between-group comparisons. (20 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Sham feeding in rats after ventromedial hypothalamic lesions and vagotomy.

Two studies examined sham feeding in female Sprague-Dawley rats with ventromedial hypothalamic (VMH) lesions with or without abdominal vagotomy. In Exp I, intact Ss consumed more than twice as much sweet milk during 1-hr tests of sham feeding as they did when feeding normally. Ss with VMH lesions showed exaggerated sham feeding, which was elevated almost four-fold over their already high normal feeding baseline. In Exp II, vagotomy substantially reduced sham feeding in Ss with VMH lesions. After vagotomy, VMH Ss sham fed half as much as nonvagotomized VMH Ss. Vagotomy did not, however, reduce sham feeding to control levels. Results are consistent with the hypothesis that VMH hyperphagia arise from exaggeration of orosensory responsiveness, which is, in part, a consequence of perturbed vagal function. (40 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of ventromedial hypothalamic lesions on conditioned sucrose aversions in rats.

Maintained 11 female Wistar rats with lesions of the ventromedial hypothalamus (VMH) at 95% body weight (BW) and gave them an intraperitoneal injection of a 2% BW dose of .15 M lithium chloride following the consumption of sucrose pellets. Control groups (N = 18) maintained at 95 and 80% BW received the same treatment. The VMH and 80% groups showed less aversion to sucrose than the 95% group. Results suggest that appetitive passive-avoidance deficits in VMH-lesioned rats may be produced by increased hunger motivation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Aggression, avoidance, and reaction to novel environments in female rats with ventromedial hypothalamic lesions.

In an experiment with 30 adult female Sprague-Dawley rats, lesions in the ventromedial hypothalamus of 20 Ss (a) increased the probability of pain-elicited aggressive responses; (b) caused a loss of dominance in a situation where fighting was elicited by food competition and territorial defense; (c) did not change interspecies aggressive reactions; (d) facilitated acquisition of avoidance responses in a shuttle box; (e) increased locomotor activity and decreased latency of feeding behaviors in novel environments; and (f) resulted in an increase in locomotor activity in response to the introduction of shock in the shuttle box, in contrast to a decrease seen in controls. (20 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Failure to obtain sex differences in development of obesity following ventromedial hypothalamic lesions in rats.

Gave 24 male and 24 female albino Charles River rats either a high-fat or a ground-food diet following ventromedial hypothalamic or sham lesions. After 63 days on 1 diet, diets were reversed for 27 days. Over 63 days (a) lesioned Ss of both sexes showed a significant increase in weight over their controls, (b) Ss on high fat gained more weight than those on ground food, and (c) there was no difference between the sexes in weight gain. When diets were reversed, lesioned Ss now on ground food maintained about the same weight as before reversal, while Ss switched to the high-fat diet rapidly increased their body weight to a point near that of Ss originally on the high-fat diet. Data indicate that there is no sex difference in weight gain following ventromedial lesions. It is suggested that previously reported differences result from (a) insufficient periods of observation, (b) offering unpalatable diets, or (c) the use of random-bred strains which increases variability of animal size and lesion placement. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Comparison of behavioral deficits caused by lesions in septal and ventromedial hypothalamic areas of female rats.

41 female Holtzman rats with lesions in ventromedial hypothalamic (VMH) area and 37 Ss with lesions in septal area were compared with 30 normal Ss for passive-avoidance performance (Exp I), reversal learning (Exp II), and spontaneous alternation (Exp III). Lesions in both septal and VMH areas produced a deficit in passive-avoidance performance, a greater number of errors in reversal learning, and reduced spontaneous alternation in a -maze. The qualitatively similar behavioral deficits produced by septal and VMH lesions suggests that at least part of the functions of both of these areas may overlap in a single system. An attempt was made to identify such a functional system, and an explanation for the behavioral deficits produced by VMH damage was offered. (20 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Preference for mode of obtaining reinforcement in rats with lesions in septal or ventromedial hypothalamic area.

Assigned 54 female Holtzman albino rats to groups receiving sham operations, septal lesions, or ventromedial hypothalamic lesions. In a choice situation where food could be obtained free or by working, lesioned Ss obtained significantly more reinforcement by bar pressing than by not working. This preference for obtaining reinforcement by bar pressing was evident in normal and operated Ss even when different amounts of effort (fixed ratios of l, 3, ll) were required to obtain reinforcement. When adulterated pellets were substituted for regular pellets, operated Ss continued to obtain significantly more reinforcement by bar pressing than normal Ss. Findings indicate the limitation of the explanation that rats with lesions in the ventromedial hypothalamus have reduced appetitive motivation or a general motivational deficit. (21 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effect of a quinine-adulterated diet upon body weight maintenance in male rats with ventromedial hypothalamic lesions.

Reports results of 3 experiments with a total of 100 male Sprague-Dawley rats. Ss offered a quinine-adulterated diet after receiving either ventromedial hypothalamic or sham lesions displayed nearly identical periods of anorexia before maintaining their body weight at a stable but reduced level. When starved prior to surgery to a body weight below this reduced maintenance level, both ventromedial hypothalamic and control Ss displayed an initial period of rapid weight gain on the quinine-adulterated diet. When subsequently offered only this diet for an 8-wk period, both groups, after castration, maintained the same reduced level of body weight. It is concluded that ventromedial hypothalamic animals overeat and become obese on palatable diets but defend the same lower weight level as controls when challenged with unpalatable diets. Impairment of a mechanism setting the upper, but not the lower, weight limit is suggested to be responsible for the greatly expanded range of body weights generated in the ventromedial hypothalamic animal by manipulation of diet palatability. (29 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Decrease in food intake following cortical spreading depression in static obese rats with ventromedial hypothalamic lesions.

Subjected 19 male and 23 female rats with ventromedial hypothalamic (VMH) lesions or with sham lesions to cortical spreading depression (CSD) 150 days after lesioning. Lesioned Ss showed a significantly lower food intake (as percentage of intake before CSD) than sham-lesioned Ss in the 14 days after CSD, but water intake did not differ between lesioned and sham-lesioned Ss. Both groups showed a slight decline in body weight, but lesioned Ss lost significantly more weight than sham-lesioned Ss. After 14 days, body weight, food intake, and water intake had returned to pre-CSD levels in both groups. Findings indicate that Ss with VMH damage are more sensitive to the effects of CSD than are normals and suggest that CSD acts to increase the activity of the VMH and to inhibit food intake, and this increase in activity is prolonged in VMH-lesioned Ss. (22 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Enhancement and suppression of self-stimulation after ventromedial hypothalamic lesions.

Investigated the effects of lesions in the ventromedial hypothalamus (VMH) upon self-stimulation in 25 male hooded Long-Evans rats. Ss trained to press a bar for lateral hypothalamic (LH) stimulation showed an enhancement of responding during the 1st 24 hrs after VMH lesioning, followed by a suppression of responding for several days. The degree of response suppression, but not enhancement, was correlated with an increase in food intake. In Ss trained to shuttle for LH stimulation, only the suppression effect was observed after VMH lesions. Barpressing for dorsal tegmental stimulation was not affected by the lesions. Results suggest that LH stimulation activates at least 2 groups of neurons: one group is specifically involved in barpressing and the other is involved equally in barpressing and shuttling. (French summary) (36 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Weight regulation with palatable food and liquids in rats with lateral hypothalamic lesions.

Maintained 25 female Carworth CFE albino rats with 4- or 7-sec 1-ma bilateral lesions of the lateral hypothalamus (LH) for 87 days on a high-fat diet and a sequence of fluids (water, 6% sucrose, and 1 or .2% saccharin). Lesioned Ss reached a greater weight than 9 sham-lesioned Ss offered the same diet and fluids, and maintained greater weight regardless of the fluid offered. These data do not support the hypothesis that LH lesions lower the set point for weight. Rather, the finickiness of LH Ss results in smaller intake of unpalatable foods and water which, in turn, results in stablization of weight below that of controls. If sufficiently hydrated, LH Ss eat greater quantities of highly palatable foods than do controls, resulting in greater body weight. (24 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Female and male sexual responses in female cats with ventromedial hypothalamic lesions.

Following preoperative testing for receptivity, proceptivity, and male mating behavior, 27 female cats received either lesions in the anterior or posterior portion of the ventromedial hypothalamus (VMH) or sham lesions. Neither of the VMH lesion placements reduced proceptivity and receptivity scores. However, the female mating pattern was significantly altered in that although females in both lesion groups initially allowed a stud male to mount, they usually did not allow the male to intromit. As in rodents, the VMH in the cat appears to be an important neural area for the display of normal female sexual behavior. Low levels of male sexual behavior were seen in the 3 groups preoperatively, and no changes were observed in the levels of male behavior following lesion placement. Thus, because lesions that disrupted female behavior did not affect male sexual behavior, it appears that the neural areas controlling homotypical and heterotypical sexual behaviors are not necessarily neurally linked. (24 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Adrenocortical response to hypertonic saline in rats with lateral hypothalamic lesions.

Used plasma corticosterone levels to assess the response to stress induced by ip injections of hypertonic saline in 27 male albino Harlan-Sprague rats with lateral hypothalamic (LH) or sham lesions. Ss with LH lesions displayed a corticosterone response equal to that of normal Ss under basal conditions, after control injections of isotonic saline, and 20 min after injection of hypertonic saline (1.5 M, 1.0 ml/100 g of body weight). The corticosterone response of Ss with LH lesions, however, was significantly less than that of normal Ss 90 min after injection of hypertonic saline when no water was available. With access to water, normal Ss displayed substantial drinking (14.5 ml/90 min), which resulted in a reduction in plasma corticosterone concentrations to a level observed after a control injection of isotonic saline, but the little water ingested by Ss with LH lesions (2.5 ml) had no effect on the pituitary-adrenal system. It is concluded that the failure of Ss with LH lesions to drink following a hydrational challenge is not the result of an exaggerated response to stress. (17 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

To be lean or not to be lean. Is leptin the answer?

Coronary heart disease (CHD) has been considered as a multifactorial disorder with the involvement of both environmental and genetic factors. The advent of tools to investigate individual variability of DNA has allowed us to perform the association studies of candidate genes. However, an association between genetic trait and phenotypic variations is not easy to demonstrate and several reported association between genetic markers and risk factors or overt CHD have gone unconfirmed. It should not be assumed that for a given genetic trait, the impact on risk will be similar in all populations. In particular, most studies of the molecular bases of CHD have involved Caucasian subjects, so much more work with the Korean population is needed before genetic testing for susceptibility to CHD can be offered to Koreans as a clinical service. In this review, we discuss two aspects of the molecular bases of CHD: i) Molecular bases of the candidate gene related to lipoprotein metabolism including apolipoprotein AI-CIII-AIV gene duster, apolipoprotein B, apolipoprotein E-CI-CII gene cluster, apolipoprotein(a), LDL receptors, lipoprotein lipase, cholesteryl ester transfer protein, and apo B editing protein; ii) Molecular bases of the candidate gene related to thrombotic and other factors including fibrinogen, factor VII, plasminogen activator inhibitor 1, homocysteine, stromelysin, paraoxonase, and angiotensin converting enzyme. Studies involving the Korean population, especially those performed by our teams, are also summarized.