Micah Leshem

Palatability: response to nutritional need or need-free stimulation of appetite?

The traditional view of palatability was that it reflected some underlying nutritional deficit and was part of a homeostatically driven motivational system. However, this idea does not fit with the common observation that palatability can lead to short-term overconsumption. Here, we attempt to re-evaluate the basis of palatability, first by reviewing the role of salt-need both in the expression of liking for salty tastes, and paradoxically, in dissociating need from palatability, and second by examining the role of palatability in short-term control of appetite. Despite the clarity of this system in animals, however, most salt (NaCl) intake in man occurs in a need-free state. Similar conclusions can be drawn in relation to the palatability of food in general. Importantly, the neural systems underlying the hedonic system relating to palatability and homeostatic controls of eating are separate, involving distinct brain structures and neurochemicals. If palatability was a component of homeostatic control, reducing need-state should reduce palatability. However, this is not so, and if anything palatability exerts a stronger stimulatory effect on eating when sated, and over-consumption induced by palatability may contribute to obesity. Differential responsivity to palatability may be a component of the obese phenotype, perhaps through sensitisation of the neural structures related to hedonic aspects of eating. Together, these disparate data clearly indicate that palatability is not a simple reflection of need state, but acts to promote intake through a distinct hedonic system, which has inputs from a variety of other systems, including those regulating need. This conclusion leads to the possibility of novel therapies for obesity based on modulation of hedonic rather than homeostatic controls. Potential developments are discussed.

Weaning age, social isolation, and gender, interact to determine adult explorative and social behavior, and dendritic and spine morphology in prefrontal cortex of rats.

We tested the effect of weaning at 21 or 30 days, followed by individual or group housing, on explorative and social behavior in adult male and female rats, and in males, on dendritic length and spine density in prefrontal cortex. In the open field, rats weaned early were the most active, while those weaned late and group housed were the most explorative. In the social interaction test, behavior in adult females was relatively impervious to weaning age or rearing condition. Isolated males sought out social interaction, whereas, group-reared males tended to avoid it. Social behaviors in males weaned early or group-reared correlated with decreased dendrite length and spine density, whereas, non-social behaviors correlated with increased dendritic length. Such changes are consistent with neural pruning in the development of social behavior. Although our experimental manipulations were mild, and serve as standard rearing conditions in many laboratories, their effects on brain and behavior were marked, and differed by gender. Early rearing conditions may have few appreciable effects when studied in isolation, but their interactive effects on adult social behavior are significant and varied.

Exercise Increases the Preference for Salt in Humans

Salt preference was evaluated in 21 male students before and after 1 h routine exercise by measuring their preferred concentration of NaCl in tomato soup. Before exercise, baseline measures of preference were similar to those of 21 matched student controls that did not exercise. Immediately after exercise, the amount of NaCl added to flavour the soup increased by approximately 50% in comparison to pre-exercise baselines and to non-exercising controls. Concentration of sugar flavouring tea was unaltered. Twelve hours after exercise, preferred concentrations of both salt in soup and of sugar in tea were elevated. There were no changes, at any of these time intervals, in the preferences of the control students that did not exercise. These delayed and non-specific changes in preferences are attributed to hunger. However, we speculate that the immediate and specific increase in NaCl preference after exercise is due to sodium loss (in perspiration) and/or sympathetic arousal that activates the hormones, aldosterone and angiotensin II in humans, and that in animals increases salt preference. Our findings provide further evidence for the physiological regulation of salt preference in humans.

Transgenerational effects of infantile adversity and enrichment in male and female rats.

To discover whether the accumulation of lifes experiences, adverse and enriching, inform, and serve the following generation by inheritance we examine whether stress to a weanling female will influence her future offspring, whether prereproductive enrichment to the dam, or postweaning enrichment to the offspring, can reverse the transgenerational effects of stress, and whether, like adversity, enrichment might have transgenerational effects. Female rats were exposed to stressors when they were 27-29 days old. Half of these females and their controls were then raised in an enriched environment from weaning until mating at 60 days to examine whether preproduction enrichment reverses the effects of preproduction stress on offspring. Half of the offspring of each group were raised in an enriched environment after weaning, to see whether it reverses the effects of preproduction stress and buttresses prereproductive enrichment. Behavior was examined in 625 adult offspring in 16 groups covering all permutations of the experimental variables (preproduction weanling stress (PS), preproduction enrichment (PE), offspring enrichment (OE), sex). Exploration, avoidance learning, startle, and social interaction were tested. Results reveal that very early prereproductive experience in females, adverse or enriching, will transgenerationally influence their future offspring, depending on the behavior tested and sex. Our finding that enrichment, whether to the parent or offspring generation, can ameliorate the transgenerational impact of adversity, has novel implications for the malleability of transgenerational inheritance, and its individual, social, and therapeutic impact.

Salt conditions a flavor preference or aversion after exercise depending on NaCl dose and sweat loss

Sodium supplementation during or after exertion improves hydration. We hypothesized that it may therefore improve well being after exercise-induced sodium loss. To avoid cognitive-biased interpretations of the taste of salt, we used untasted salt in swallowed capsules to condition preference for the flavor of a drink. In four 90 min exercise sessions, 2-3 days apart, participants drank 100 ml of a novel drink and swallowed a capsule, either empty (placebo), or containing 200, 400 or 600 mg NaCl (n=20 in each group). We found both increases and decreases in flavor preference conditioning, depending on salt dose and level of sweat loss: in groups receiving salt supplementation, high levels of sweat loss induced greater flavor conditioning of preference than low levels of sweating. However, 600 mg NaCl conditioned a flavor aversion relative to placebo, which was greater in exercisers sweating little. We conclude that since untasted salt conditioned flavor preference in direct proportion to the amount of sweat lost, replenishment of the sodium lost in sweat induces a rewarding physiological state. The results provide further evidence for the physiological determinants of human salt appetite, and buttress the evidence that post-ingestive effects condition food preferences. Conditioned flavor preference may also provide a useful measure of the benefits of other nutrient additives in sports drinks.

Prereproductive Stress to Female Rats Alters Corticotropin Releasing Factor Type 1 Expression in Ova and Behavior and Brain Corticotropin Releasing Factor Type 1 Expression in Offspring

BACKGROUND Human and animal studies indicate that vulnerability to stress may be heritable and that changes in germline may mediate some transgenerational effects. Corticotropin releasing factor type 1 (CRF1) is a key component in the stress response. We investigated changes in CRF1 expression in brain and ova of stressed female rats and in the brain of their neonate and adult offspring. Behavioral changes in adulthood were also assessed. METHODS Adult female rats underwent chronic unpredictable stress. We extracted mature oocytes and brain regions from a subset of rats and mated the rest 2 weeks following the stress procedure. CRF1 expression was assessed using quantitative reverse-transcription polymerase chain reaction. Tests of anxiety and aversive learning were used to examine behavior of offspring in adulthood. RESULTS We show that chronic unpredictable stress leads to an increase in CRF1 messenger RNA expression in frontal cortex and mature oocytes. Neonatal offspring of stressed female rats show an increase in brain CRF1 expression. In adulthood, offspring of stressed female rats show sex differences in both CRF1 messenger RNA expression and behavior. Moreover, CRF1 expression patterns in frontal cortex of female offspring depend upon both maternal and individual adverse experience. CONCLUSIONS Our findings demonstrate that stress affects CRF1 expression in brain but also in ova, pointing to a possible mechanism of transgenerational transmission. In offspring, stress-induced changes are evident at birth and are thus unlikely to result from altered maternal nurturance. Finally, brain CRF1 expression in offspring depends upon gender and upon maternal and individual exposure to adverse environment.

Unpredictable chronic stress in juvenile or adult rats has opposite effects, respectively, promoting and impairing resilience

We evaluated the effects of early maternal deprivation (MD; age 7–14 days) alone or in combination with unpredictable chronic stress (UCS; MDUN; 28–84 days) on anxiety and learning in 90 days old adult rats. We hypothesized that exposure to both stressors (MDUN) would be more detrimental than exposure to one or neither. Unexpectedly, adult rats from the MDUN group did not differ from control animals, whereas adult MD animals exhibited impaired avoidance learning. We next investigated the effect of juvenile-onset (30–90 days) versus adult-onset (60–90 days) stress on avoidance learning in adulthood (90 days). We found that adult-onset chronic stress impaired avoidance learning and memory whereas juvenile-onset stress did not. Thus, the results again indicate that juvenile exposure to UCS induces resilience rather than impairment.

Refinement of dendritic and synaptic networks in the rodent anterior cingulate and orbitofrontal cortex: Critical impact of early and late social experience

The process of weaning programs the neurobehavioral development and therefore provides a critical formative period for adult behavior. However, the neural substrates underlying these behavioral changes are largely unknown. To test the hypothesis that during childhood neuronal networks in the prefrontal cortex are reorganized in response to the timing and extent of social interactions, we analyzed the length, ramification, and spine density of apical and basal dendrites of layer II/III pyramidal neurons in four groups of male rats. (1) Early weaning at postnatal day (PND) 21 + postweaning social rearing (EWS), (2) late weaning at PND 30 + postweaning social rearing (LWS), (3) early weaning + postweaning social isolation (EWI), (4) late weaning + postweaning social isolation (LWI). Compared with late weaned animals, the early weaned animals displayed elevated spine densities on apical and basal dendrites only in the anterior cingulate (ACd), but not in the orbitofrontal cortex (OFC), irrespective of the postweaning housing conditions. For dendritic length and complexity an interaction between the factors weaning and postweaning rearing conditions was observed. In the ACd the EWI animals had longer and more complex apical dendrites compared with all other groups, whereas in the OFC the EWI animals displayed a significant reduction of apical dendritic length and complexity compared with the EWS group. Taken together, our findings show that the timing as well as the amount of social contact with family members significantly affects the refinement of prefrontal cortical synaptic networks, which are essential for emotional and cognitive behavior.

Adversity before Conception Will Affect Adult Progeny in Rats.

The authors investigated whether adversity in a female, before she conceives, will influence the affective and social behavior of her progeny. Virgin female rats were either undisturbed (controls) or exposed to varied, unpredictable, stressors for 7 days (preconceptual stress [PCS]) and then either mated immediately after the end of the stress (PCS0) or 2 weeks after the stress ended (PCS2). Their offspring were raised undisturbed until tested in adulthood. PCS offspring showed reduced social interaction; in the acoustic startle test, PCS males were less fearful, whereas PCS females were more fearful; in the shuttle task, PCS0 males avoided shock better; and in the elevated maze, PCS0 females were more active and anxious. The 2-week interval between stress and mating assuaged the effects on offspring activity and shock avoidance but not the changes in social behavior and fear in male and female offspring. Hence, PCS to the dam, even well before pregnancy, influences affective and social behavior in her adult offspring, depending on how long before conception it occurred, the behavior tested, and sex. (PsycINFO Database Record (c) 2009 APA, all rights reserved).

The ontogeny of salt hunger in the rat.

Salt hunger is the behaviour of an animal suffering sodium deficiency. It is characterised by an increased motivation to seek and ingest sodium, and the ability to distinguish between sodium and other salts. Here I review the development of salt hunger in the rat. Salt hunger develops rapidly between birth and weaning. It can first be demonstrated 72 h postnatally when an intracerebroventricular injection of renin elicits greater swallowing of NaCl solution than water and greater mouthing of solid fragments of NaCl than of an artificial sweetener. However, sodium deficit per se cannot arouse the hunger at this age, and first elicits increased intake of NaCl only at 12 days-of-age. The next landmark is at 17 days-of-age when the hormonal synergy of aldosterone and central angiotensin II first elicits salt hunger, as it does in the adult. The specificity of the hunger for the sodium ion also develops postnatally: the 72 h-old sodium-hungry neonate does not distinguish between NaCl and other mono- and di-valent chloride salts but, increasingly during development, the sodium hungry pup distinguishes salts and by weaning age NaCl is clearly preferred to other salts almost as it is in adults. Early development may also be a sensitive period for determining lifelong preferences, and indeed, acute perinatal sodium depletion induces a lifelong enhancement of salt intake. Taken together, these findings demonstrate how a behaviour develops precociously and how, when the behaviour becomes important at weaning, the rat pup is competent to meet its sodium requirements, and may be adapted to anticipate sodium deficit.