Inhibitory avoidance deficit following short-term adrenalectomy in the rat: the role of adrenal catecholamines

Impaired retention of an inhibitory avoidance response was observed in rats subjected to adrenalectomy (ADX) up to 120 hr before the single learning trial. Corticosterone substitution failed to normalize this behavioral deficit. Rats ADX 240 hr prior to the learning trial showed a normalized behavior. Adrenomedullectomy (ADXM) 48 or 240 hr before learning caused a similar impairment as in short-term ADX rats. The 240-hr ADX rats subjected to corticosterone substitution showed the same behavioral deficit as short-term ADX rats or ADXM ones. Immediate postlearning subcutaneous injection of adrenaline in a dose range of 0.005-5.0 micrograms/kg or of noradrenaline (0.005-0.5 microgram/kg) to 48-hr ADX rats resulted in a dose-related improvement of later retention behavior. Higher doses of catecholamines were less or ineffective. Postlearning treatment of 48-hr ADXM rats with adrenaline (0.5-500 micrograms/kg) caused a similar pattern of behavioral changes. It is concluded that adrenal catecholamines play an important role in the modulation of consolidation of memory. In addition, the high circulating ACTH levels that follow long-term ADX may correct for the behaviorial deficit induced by the absence of adrenomedullary catecholamines.     

The relationship between adrenal steroids and enrichment-induced brain growth.

The question of whether brain growth brought about by environmental enrichment is mediated by the adrenal cortex has not been answered. Accordingly, young male rats were either adrenalectomized (ADX) and infused with a constant maintenance dose of corticosterone (2 mg.kg-1.day-1) or sham-operated and implanted with a blank infusion device. Half of each surgical group was maintained in either impoverished (IC) or enriched conditions (EC). After 30 days, changes in forebrain growth and thickness of various cortical and subcortical regions were determined for each group. Enrichment and ADX independently increased forebrain weight and thickened cortical tissue at about the same anatomical sites. However, combined treatments were additive, not interactive. EC-induced brain growth is mimicked but not mediated by adrenalectomy.     

Accelerated development of cardiac sympathetic responses in spontaneously hypertensive (SHR) rats

The functional development of cardiac and adrenal medullary responses to reflex activation of the sympathetic nervous system was studied in preweanling spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) normotensive rats. Pups of the two strains received injections of insulin or saline at 2, 4, 8, 12, or 16 days of age and were sacrificed 3 h later. Insulin administration produces a significant decrease in circulating levels of glucose which in turn results in a centrally mediated increase in sympathetic outflow. The induction of ornithine decarboxylase (ODC) in heart and the depletion of epinephrine from the adrenal medulla served as tissue markers of functional sympathetic neurotransmission. WKY and SHR pups had comparable levels of ODC activity in heart under basal conditions. In contrast, levels of catecholamines in the adrenals were greater in SHR pups at 2 and 4 days of age. Following insulin administration, SHR pups exhibited a greater induction of cardiac ODC activity at 2, 4, and 8 days of age compared to age-matched WKY controls. However, there were no differences between SHR and WKY pups in the magnitude of the adrenal medullary response to insulin-induced hypoglycemia. These alterations in sympathetic-target tissue development during the first postnatal week of life may contribute in part to the higher arterial pressures maintained by SHRs throughout the lifespan.     

Homeostatic disruption and memory: effect of insulin administration in rats

The present study examined the effect of insulin-induced hypoglycemia on 24-h retention of passive avoidance in rats. In the initial experiment, rats received either insulin (50 U/kg) or saline injections 30 min prior to training and testing. Impairments in retention were observed when animals were trained with insulin and tested with saline. This anterograde memory loss was attenuated, however, when insulin was administered prior to both training and testing. A subsequent experiment further explored the disruptive effect of hypoglycemia on memory. Data from this study indicated that lower doses of insulin at training (5 and 10 U/rat) yielded impairments in 24-h retention of passive avoidance. It is concluded that disruption of glucoregulation can produce state-dependent anterograde memory losses in rats. Possible implications for the effects of hypoglycemia on cognitive functioning in humans are discussed.     

Single, but not multiple pairings of sucrose and corticosterone enhance memory for sucrose drinking and amplify remote reward relativity effects

This study tested whether pre-training pairings of ingestion of a 32% sucrose solution and injection(s) of corticosterone (B) would enhance later ingestion in the absence of B, and whether these effects would carry over into later contrast-like effects when animals were subsequently shifted to 4% sucrose. Frequency-dependence of these pairings was also examined. Three groups of male Sprague-Dawley rats were adrenalectomized (ADX). A fourth group was sham ADX. Each ADX group received three presentations of sucrose and B (666 microg/kg, s.c.). One received unpaired presentations (separated by days), one received two unpaired presentations and one paired (i.e., simultaneous) presentation, and one received three paired presentations. Shams received three sucrose presentations paired with saline. Single, but not multiple pairings of B with ingestion of a 32% sucrose solution enhanced later sucrose ingestion, a memorial-like effect that carried over into later, opposite contrast-like effects upon presentation of a less-preferred 4% sucrose solution. These effects could not be easily ascribed to differences in training, other than the pairing regimen itself, nor to motivational differences at the time of testing, and were presumed to be memorial. The pairing and frequency-dependence of these appetitive phenomena are analogous to what is frequently observed during acute or chronic exposure to aversive situations and/or neuromodulatory stress hormones, in terms of their bidirectional effects on memory. Through effects on memory, stress hormones may modulate reward and reward relativity.     

Body Weight Reduction by Water Deprivation and Schedule-Induced Phenomena

On of the most important factors in the generation of schedule induced polydipsia, and schedule induced self-injection of drugs is the prior reduction of the animals' body weight to 80% of their free-feeding weight by food deprivation. It is suggested that reductio of body weight to 80% by water deprivation should produce similar results. The series of experiments reported here showed that rats reduced to 80% body weight by water deprivation did not develop either schedule-induced polydipsia or schedule induced wheelrunning. The results thus suggest that body weight reduction may not be a critical condition in the development of schedule-induced phenonmena.     

BOLD response to semantic and syntactic processing during hypoglycemia is load-dependent

This study investigates how syntactic and semantic load factors impact sentence comprehension and BOLD signal under moderate hypoglycemia. A dual session, whole brain fMRI study was conducted on 16 healthy participants using the glucose clamp technique. In one session, they experienced insulin-induced hypoglycemia (plasma glucose at ∼50 mg/dL); in the other, plasma glucose was maintained at euglycemic levels (∼100 mg/dL). During scans subjects were presented with sentences of contrasting syntactic (embedding vs. conjunction) and semantic (reversibility vs. irreversibility) load. Semantic factors dominated the overall load effects on both performance (p < 0.001) and BOLD response (p < 0.01, corrected). Differential BOLD signal was observed in frontal, temporal, temporo-parietal and medio-temporal regions. Hypoglycemia and syntactic factors significantly impacted performance (p = 0.002) and BOLD response (p < 0.01, corrected) in the reversible clause conditions, more extensively in reversible-embedded than in reversible-conjoined clauses. Hypoglycemia resulted in a robust decrease in performance on reversible clauses and exerted attenuating effects on BOLD unselectively across cortical circuits.The dominance of reversibility in all measures underscores the distinction between the syntactic and semantic contrasts. The syntactic is based in a quantitative difference in algorithms interpreting embedded and conjoined structures. We suggest that the semantic is based in a qualitative difference between algorithmic mapping of arguments in reversible clauses and heuristic linking in irreversible clauses. Because heuristics drastically reduce resource demand, the operations they support would resist the load-dependent cognitive consequences of hypoglycemia.     

Dexamethasone Does Not Prevent Seven-Day ADX-Induced Apoptosis in the Dentate Gyrus of the Rat Hippocampus

Long-term adrenalectomy (ADX) is known to result in apoptosis within the dentate gyrus of the rat hippocampus. While the underlying mechanism is still unclear, adrenal steroids appear to play a pivotal role in granule cell survival, as administration of the mineralocorticoid receptor (MR) agonists, corticosterone and aldosterone, to ADX rats results in protection against the ADX-induced effect. The consequence of administration of the glucocorticoid receptor (GR) agonists, dexamethasone and RU28362, however, is less clear, and either complete or only partial protection for the ADX animal has been reported. This study investigated further the role played by GR in the degenerative process. After establishing the characteristics of seven-day ADX-induced apoptosis in the young male Wistar rat, the effect of chronically-implanted, subcutaneous pellets containing various doses of dexamethasone and corticosterone, on ADX-induced apoptosis was studied. Both high and low doses of corticosterone were found to be protective. In contrast to some other studies, however, neither dose of dexamethasone had any obvious protective effect and rather seemed to increase apoptosis in dentate gyrus of intact animals. Intracerebroventricular infusion of dexamethasone for seven days was also found to be ineffective in preventing apoptosis, demonstrating that it is occupation of MR, rather than GR, which is crucial to dentate gyrus granule cell survival.     

The effect of adrenalectomy on Fos expression in vasopressinergic and oxytocinergic neurons in response to stress in the rat

This study evaluated the responses of vasopressin (AVP) and oxytocin (OT) neurons to alterations in hypothalamo-pituitary axis activity by adrenalectomy (ADX) or after restraint stress compared with basal conditions. Wistar male rats were perfuse-fixed by cardiac perfusion under anesthesia 3 h, 1, 3 and 14 days after ADX or Sham surgery. Coronal hypothalamic sections were used for evaluation of Fos, AVP and OT expression by immunohistochemistry. Under basal conditions and after stress, Fos-AVP double labeling showed no difference in the magnocellular subdivisions of the paraventricular nuclei (PVN) or in the supraoptic nuclei (SON), suggesting that the magnocellular AVP system is unlikely to contribute to ACTH secretion after restraint in both Sham and ADX rats. Fos-AVP double labeling in the parvocellular medial paraventricular nucleus (PaMP) in ADX groups was increased after 3 h in basal conditions, and in all periods after restraint stress. There were no differences between Sham and ADX groups in Fos-OT double labeling in any subdivision of the PVN; however, in the SON, the number of Fos-OT double labeled cells was increased at all time-points after stress in the ADX group. Fos expression was increased in the PaMP after 3 h and after restraint stress in the Sham and ADX groups, especially in the ADX group. In conclusion, Fos expression in different cell populations of the PVN can be differentially regulated by short- and long-term absence of glucocorticoid negative feedback and also by stress-related excitatory and/or inhibitory neural inputs. The Fos-AVP double labeling findings in the PaMP also indicate a minor participation of these vasopressinergic neurons in the regulation of the HPA axis after ADX.     

Palatability shift of a salt-associated incentive during sodium depletion

Previous studies of natural palatability-sensitive reactions, elicited from rats by tastes, have indicated that the taste of concentrated NaCl becomes more palatable during states of body sodium depletion. A training procedure based upon “sensory preconditioning” or “irrelevant incentive” designs was used here to establish gustatory conditioned labels (quinine or citric acid) for either NaCl or fructose while rats were in a normal physiological state. Experiment 1 replicated demonstrations by others that gustatory conditioned labels for salt can attract and act as independent incentives during the salt appetite induced by sodium depletion. Experiment 2 used the taste reactivity measure to show that the enhanced palatability of the taste of NaCl transfers to produce enhanced palatability of the taste of the isolated conditioned label for salt in a state-dependent fashion. These results offer further support for the proposition that conditioned incentives not only predict hedonic events to follow, but themselves become attributed with the hedonic properties of their reinforcers.     

Adrenalectomy Causes Oxidative Damage and Monoamine Increase in the Brain of Rats and Enhances Immobilization Stress-Induced Oxidative Damage and Neurotransmitter Changes

The paradox that increased levels of glucocorticoids can either enhance or suppress the organism's defense against stress, has been an obstacle to formulating a unified picture of glucocorticoid function. To clarify the glucocorticoid paradox, we examined male Sprague-Dawley rats exposed to immobilization stress and/or bilateral adrenalectomy (ADX), and measured oxidative damage to lipid, protein, and DNA, as well as monoamine neurotransmitter turnover. ADX, which is similar to stress, induces an increase in lipid peroxidation and protein oxidation, accompanied by increased monoamine neurotransmitter turnover in several regions of the brain of rats. The effect of ADX is greater than that induced by short-term immobilization stress. In addition, ADX enhances stress-induced oxidative damage and increase of monoamine neurotransmitter turnover. These results, together with our previous finding that long-term stress causes oxidative damage to the brain, suggest that stress levels of glucocorticoids, or levels lower than basal, cause oxidative damage. However, basal levels of glucocorticoids appear to buffer against oxidative damage. These findings provide possible mechanisms to understand the glucocorticoid paradox, and support the stress-oxidative hypothesis of aging acceleration.     

The Irreflexivity Of Brouwer's Philosophy

I argue that Brouwer's general philosophy cannot accountfor itself, and, a fortiori, cannot lend justification tomathematical principles derived from it. Thus it cannot groundintuitionism, the jobBrouwer had intended it to do. The strategy is to ask whetherthat philosophy actually allows for the kind of knowledge thatsuch an account of itself would amount to.     

A neural activity interpretation of luminance effects on infant pattern preferences

Visual pattern preferences were established for 9- and 13-week-old infants (N = 96) using stimuli varying in contour density presented either at a low, moderate, or high luminance level. Age differences in the maximally preferred patterns across stimuli and luminance levels indicated that luminance interacts with contour density in determining stimulus preference functions for a given age. A neural activation model based on synchronous neural activity was advanced to describe these results.     

Extinction of Within-event Learning Is Contextually Controlled and Subject to Renewal

Five experiments examined within-event learning in rats by inducing an appetite for one of the elements (salt) of a compound stimulus and assessing preference for the other element (almond). Almond preference was conditional upon (1) the almond flavour having been presented in compound with the salt, and (2) the assessment being conducted when the rats were out of sodium balance (Experiment 1). Presentations of the compound in one environment (A) and of the salt and almond elements in a second environment (B) resulted in greater almond preference when rats were tested in A than in B (Experiment 2). Almond preference was reduced when separate presentations of the compound and almond (Experiment 3) or of the compound and salt (Experiment 4) occurred in the same environments but not when these presentations occurred in different environments. Rats exposed to the compound in A and then extinguished to the elements in either A or B showed a reduced almond preference when tested in the extinction environment, but not when tested in the other environment (Experiment 5). Thus, extinction of within-event learning is context-specific and subject to renewal. The results were interpreted in terms of an associative model whereby separate presentations of the elements result in a symmetrical inhibitory link which is contextually gated (Bouton, 1993).     

Social interaction modifies learned aversions, sodium appetite, and both palatability and handling-time induced dietary preference in rats (Rattus norvegicus)

In a series of four experiments, I examined the extent to which socially transmitted diet preference could counteract the effects of a learned aversion (Experiment 1), a palatability-based diet preference (Experiment 2), a polyethylene glycol 20,000-induced sodium appetite (Experiment 3), and a handling-time induced dietary preference (Experiment 4). I found that rats poisoned after eating a novel diet ate very substantial amounts of the averted diet following interaction with conspecifics that had eaten the averted diet. Following interaction with conspecifics that had eaten an unpalatable diet, rats offered a choice between palatable and unpalatable diets ate more than twice as much unpalatable diet as did controls lacking social experience. Sodium-deficient rats offered a choice between sodium-enriched and sodium-adequate diets ate less than half as much sodium-enriched diet, following interaction with conspecifics that had eaten sodium-adequate diet as did control rats lacking social experience. Rats offered a choice between isocaloric, roughly equipalatable foods with long and short handling times (e.g., sunflower seeds with and without shells) chose the food having the longer handling time after interacting with conspecifics eating that food. These findings suggest that social influence is a major factor in guiding diet selection by rats.     

Extinction and latent inhibition of within-event learning are context specific

Exposure to a solution composed of an odor (almond) and a taste (salt) produced a context-independent preference when rats were subsequently tested with almond under a salt appetite. Postcompound exposure to either the almond or the salt alone reduced almond preferences but only when rats were tested in the extinction context. Exposure to either the almond or the salt in 1 context in advance of exposure to the compound in a different context also reduced preferences but only when the rats were tested in the context in which the element had been pre-exposed. These results show that extinction and latent inhibition of within-event learning are context specific.     

Incentive properties of sucrose and saccharin under different deprivation conditions

In Expt 1 it was found that hungry rats developed a 100% preference for 8% sucrose over water in a maze-choice situation, whereas thirsty rats developed no preference. When deprivation conditions for the two groups were reversed the pattern of preference relations also reversed. In a 2nd experiment nondeprived rats developed a preference for either 8% sucrose or 0.2% saccharin over water while thirsty Ss did not develop a preference for either of these over water. The results are discussed in terms of incentive theory.     

Polydipsia induced by a schedule of brain stimulation reinforcement

Rats pressed a lever for a signaled brain stimulation reinforcement on either fixed-interval or fixed-ratio schedules. Both schedules induced polydipsia, with a median water intake of 22.5 ml (about four times the control level) in 3-hr sessions. The stimulation did not directly elicit drinking or other behaviors. In a second experiment, two out of four rats became polydipsic during extinction following a continuous schedule of brain stimulation reinforcement. The results were compared with previous attempts to induce polydipsia with a schedule of brain stimulation reinforcement and were discussed in terms of polydipsia as a model of human “compulsive” behaviors.     

Corticosterone effects on BDNF mRNA expression in the rat hippocampus during morris water maze training

Corticosterone and Brain-Derived Neurotrophic Factor (BDNF) have both been shown to be involved in spatial memory formation in rats. In the present study we have investigated the effect of corticosterone on hippocampal BDNF mRNA expression after training in the Morris water maze in young adult Wistar rats. Therefore, we first studied BDNF mRNA levels in the hippocampus in relation to corticosterone levels at several time points after 4 training trials in the Morris water maze. Corticosterone levels were significantly increased after this procedure, and hippocampal BDNF mRNA levels only displayed a minor change: an increase in CA1 at 1 hr after training. However, in a previous study we observed dramatically decreased hippocampal BDNF mRNA levels in dentate gyrus and CA1 at 3 hr after injection of corticosterone. In order to analyze this discrepancy, we subsequently investigated if hippocampal BDNF mRNA expression is affected by corticosterone at 3 hr after water maze training. Therefore, we incorporated ADX animals and ADX animals which were injected with corticosterone in our study. ADX animals which were subjected to water maze training displayed similar hippocampal BDNF mRNA levels 3 hr after training compared to control ADX animals. Furthermore, ADX animals which were injected with corticosterone showed decreased BDNF mRNA levels in all hippocampal regions compared to control ADX animals. Water maze training did not alter this effect. Thus, the increased corticosterone levels during water maze training do not affect hippocampal BDNF mRNA expression, although exogenous corticosterone is effective under these conditions. Hence, our results suggest that in this situation BDNF is resistant to regulation by endogenous corticosterone, which may be important for learning and memory processes.     

Stress-induced Fos-like Immunoreactivity in the Pons and the Medulla Oblongata of Rats

Immunoreactivity of the immediate early gene c-fos was used to investigate changes in the activity of brainstem neurons in response to acute stressors like immobilization, formalin-induced pain, cold exposure, hemorrhage and insulin-induced hypoglycemia. Different stressors induced Fos-like immunoreactivity in different pontine and medullary neurons. A single, 3 hour immobilization was found to be a very strong stimulus that activated brainstem catecholaminergic (tyrosine hydroxylase-immunopositive) neurons and cells in the raphe and certain pontine tegmental nuclei, as well as in the reticular formation. Pain, induced by a subcutaneous injection of formalin was also effective on catecholamine-synthesizing neurons and on others cells in the nucleus of the solitary tract. Cold exposure activated cells mainly in the sensory spinal trigeminal and parabrachial nuclei and in the so-called "pontine thermoregulatory area". Moderate Fos-like immunoreactivity was induced by a hypotonic (25%) hemorrhage in medullary catecholaminergic neurons, the nucleus of the solitary tract and the Barrington nucleus. Among stressful stimuli used, insulin-induced hypoglycemia elicited the smallest Fos activation in the lower brainstem. The present observations indicate that different stressors may use different neuronal pathways in the central organization of the stress response.