RELATIONSHIP between prandial drinking behavior and supersensitivity of salivary glands after superior salivatory nucleus lesions in RATS.

Prandial drinking, an increase in the number of drinking responses and secondary or non-homeostatic polydipsia in the presence of dry food, is typically associated with a deficit in salivary secretion. This study investigates the degree of salivary gland supersensitivity to pilocarpine administration after lesions to the superior salivatory nucleus (SSN), the site of origin of the parasympathetic preganglionic neurons that innervate the submandibular-sublingual (S-S) salivary glands. The main aim was to determine if there is a relationship between the degree of glandular supersensitivity, as an index of secretory deficit, and the development of prandial drinking in lesioned rats. Results showed that following SSN lesions two subgroups of rats were obtained. One subgroup exhibited prandial drinking but the other was similar to the control group. The SSN-lesioned prandial drinking subgroup presented significantly greater supersensitivity than the SSN-lesioned non-prandial drinking rats; the non-prandial drinking subgroup, in turn, presented significantly more supersensitivity than controls. Additionally, S-S supersensitivity observed in rats that exhibited prandial drinking due to the sectioning of chorda tympani efferent axons was compared to that observed in rats exhibiting prandial drinking due to SSN lesions. It was found that both groups presented the same S-S supersensitivity curve. These results indicate that SSN lesions produce a gradation of S-S supersensitivity values that appear to run parallel to the degree of glandular secretory deficit caused by the lesions. Thus, only the rats with greater secretory deficit (greater supersensitivity) develop prandial drinking. These data support the idea that there is in fact a functional link between the lateral reticular formation of the brainstem (the region associated with the SSN) and S-S salivary glands.

Place preferences induced by electrical stimulation of the external lateral parabrachial subnucleus in a sequential learning task: Place preferences induced by NLPBe stimulation.

It is known that electrical stimulation of the external lateral parabrachial nucleus (NLPBe) can sustain concurrent taste and place learning. Place preferences can be learned through different procedures. Previous studies demonstrated that electrical stimulation of the PBNLe can generate aversive and preference place learning using concurrent procedures. In the concurrent procedure, the animals can move freely in the maze, and intracranial electrical stimulation is associated with their voluntary stay in one of the two maze compartments. However, the rewarding properties of most stimuli, whether natural or drugs of abuse, have usually been investigated using the sequential procedure, in which animals are confined while receiving the unconditioned stimulus and then undergo a choice test without stimulation in a later phase. This study examined whether this stimulation can sustain place preference learning in sequential tasks. Results demonstrated that place preferences can also be induced by the electrical stimulation of the NLBe using sequential procedures. These findings suggest that the NLPBe may form part of a brain reward axis that shares certain characteristics with those observed in the processing of natural rewarding agents and especially of drugs of abuse.

Effects of oxytocin administration on the hydromineral balance of median eminence-lesioned rats.

In the clinical setting, acute injuries in hypothalamic mediobasal regions, along with polydipsia and polyuria, have been observed in patients with cerebral salt wasting (CSW). CSW is also characterised by hypovolaemia and hyponatraemia as a result of an early increase in natriuretic peptide activity. Salt and additional amounts of fluid are the main treatment for this disorder. Similarly, experimental lesions to these brain regions, which include the median eminence (ME), produce a well-documented neurological model of polydipsia and polyuria in rats, which is preceded by an early sodium excretion of unknown cause. In the present study, oxytocin (OT) was used to increase the renal sodium loss and prolong the hydroelectrolyte abnormalities of ME-lesioned animals during the first few hours post-surgery. The objective was to determine whether OT-treated ME-lesioned animals increase their sodium appetite and water intake to restore the volume and composition of extracellular body fluid. Electrolytic lesion of the ME increased water intake, urinary volume and sodium excretion of food-deprived rats and also decreased urine osmolality and estimated plasma sodium concentration. OT administration at 8 hours post-surgery reduced water intake, urine output and plasma sodium concentration and also increased urine osmolality and urine sodium excretion between 8 and 24 hours post-lesion. From 24 to 30 hours, more water and hypertonic NaCl was consumed by OT-treated ME-lesioned rats than by physiological saline-treated-ME-lesioned animals. Food availability from 30 to 48 hours reduced the intake of hypertonic saline solution by ME/OT animals, which increased their water and food intake during this period. OT administration therefore appears to enhance the natriuretic effect of ME lesion, producing hydroelectrolyte changes that reduce the water intake of food-deprived animals. Conversely, the presence of hypertonic NaCl increases the fluid intake of these animals, possibly as a result of the plasma sodium depletion and hypovolaemic states previously generated. Finally, the subsequent increase in food intake by ME/OT animals reduces their need for hypertonic NaCl but not water, possibly in response to osmotic thirst. These results are discussed in relation to a possible transient activation of the ME with the consequent secretion of natriuretic peptides stored in terminal swellings, which would be augmented by OT administration. Electrolytic lesion of the ME may therefore represent a useful neurobiological model of CSW.

Differential rewarding effects of electrical stimulation of the lateral hypothalamus and parabrachial complex: Functional characterization and the relevance of opioid systems and dopamine.

BACKGROUND: Since the discovery of rewarding intracranial self-stimulation by Olds and Milner, extensive data have been published on the biological basis of reward. Although participation of the mesolimbic dopaminergic system is well documented, its precise role has not been fully elucidated, and some authors have proposed the involvement of other neural systems in processing specific aspects of reinforced behaviour. AIMS AND METHODS: We reviewed published data, including our own findings, on the rewarding effects induced by electrical stimulation of the lateral hypothalamus (LH) and of the external lateral parabrachial area (LPBe) - a brainstem region involved in processing the rewarding properties of natural and artificial substances - and compared its functional characteristics as observed in operant and non-operant behavioural procedures. RESULTS: Brain circuits involved in the induction of preferences for stimuli associated with electrical stimulation of the LBPe appear to functionally and neurochemically differ from those activated by electrical stimulation of the LH. INTERPRETATION: We discuss the possible involvement of the LPBe in processing emotional-affective aspects of the brain reward system.

Increased short­term food intake after external lateral parabrachial subnucleus lesions in rats.

The vagus nerve and several brainstem nuclei to which it projects have been closely associated with food intake. The aim of this study was to determine the degree to which the same or different information on food intake is processed by this nerve and by one of these nuclei, the external lateral parabrachial subnucleus (LPbNe). For this purpose, we analyzed the solid and liquid food intake of Wistar rats subjected to vagal deafferentation with capsaicin or lesions of the LPbNe. Vagotomized animals consumed significantly larger amounts of solid food during the first 24 h post­surgery but not at 48, 72, or 96 h. Animals with LPbNe lesions also consumed larger amounts of liquid and solid foods but only during periods of 60 min on day 5 and 90 min on day 6 post­surgery, respectively. According to these findings, both the vagus nerve and the LPbNe appear to be involved in short­term regulation of food intake, although they participate over different time scales. These data are discussed in terms of the potential importance of the vagal­parabrachial axis in the rapid processing of nutritional information from the upper gastrointestinal tract.

Tolerance to rewarding brain electrical stimulation: Differential effects of contingent and non-contingent activation of parabrachial complex and lateral hypothalamus.

Electrical stimulation of the parabrachial complex and related insular cortex induces concurrent conditioned place preference (CPP) in a naloxone-dependent manner. Furthermore, repeated rewarding activation of these regions generates tolerance, i.e., a reduction of the reinforcing effect. This study examined the effects of contingent and non-contingent stimulation in a CPP task. In the former modality, the animals can voluntarily select areas of the maze and thereby determine whether or not they receive stimulation. In the non-contingent procedure, the animals passively receive the administration of the rewarding electrical current while confined in the preferred place. Tolerance to the rewarding stimulation was observed in the non-contingent procedure, in which the external lateral parabrachial subnucleus (LPBe) was stimulated in a behaviorally passive task, but not in the contingent procedure. In contrast, no tolerance was observed in the group receiving rewarding stimulation of the lateral hypothalamus after either contingent or non-contingent brain activation. These findings are discussed in terms of the rewarding effects induced after contingent or non-contingent administration of electrical or chemical rewarding agents.

Tiapride prevents the aversive but not the rewarding effect induced by parabrachial electrical stimulation in a place preference task.

The parabrachial complex has been related to the processing of both rewarding and aversive signals. This pontine area is activated after the gastrointestinal administration of rewarding nutrients, in taste aversion learning, and in response to the reinforcing and aversive effects of some drugs of abuse. Electrical stimulation of this region can induce, in different animals, preference or aversion behaviors towards a place in a rectangular three-chamber maze task. This study examined the effect of tiapride, a D2/D3 receptor antagonist, on the aversive or rewarding effects induced by electrical stimulation of the external lateral parabrachial subnucleus (NLPBe). As previously observed, administration of tiapride interrupted the aversive effect induced by NLPBe electrical stimulation. However, in contrast to the effects of dopamine antagonists on other rewarding systems, tiapride did not impair the place preference induced by NLPBe stimulation, an activation effect that is subject to tolerance. Tiapride administration also appeared to have no effect on the horizontal motor activity (crossings) of the electrically stimulated animals. We discuss the specific relevance of parabrachial reward with respect to other reinforcing brain components or systems, especially in relation to the preference effect of drugs of abuse, such as opiates, after dopamine antagonist administration.

Relevance of the nucleus of the solitary tract, gelatinous part, in learned preferences induced by intragastric nutrient administration.

Food preferences have been investigated in Wistar rats utilizing a learned concurrent flavor preference behavioral procedure. Previous studies have demonstrated that the perivagal administration of neurotoxin capsaicin disrupts the learning of preferences induced by intragastric administration of rewarding nutrients (pre-digested milk). The vagus nerve projects almost exclusively towards the nucleus of the solitary tract (NST), a brain medullary gateway for visceral signals. The objective of this study was to investigate the participation of the lateral portion of the dorsomedial region, the gelatinous subnucleus (SolG), in the learning of a concurrent preference task. Results show that unlike neurologically intact animals, which learn this task correctly, animals lesioned in the gelatinous part of NST manifest a disruption of discrimination learning. Thus, intakes of the flavored stimulus paired with predigested liquid diet and of the flavored stimulus paired with physiological saline were virtually identical. However, SolG- and sham-lesioned groups consumed similar total amounts of both flavors. These findings suggest that SolG, as a relay of the vagus nerve, along with its anatomical projection, the external lateral parabrachial subnucleus (LPBe), may constitute an anatomical axis that is important in the induction of concurrent flavor/side preferences. It also appears to be relevant in other behavioral processes that require rapid processing of information from the upper gastrointestinal tract.

Disruption of re-intake after partial withdrawal of gastric food contents in rats lesioned in the gelatinous part of the nucleus of the solitary tract.

Sensory information from the upper gastrointestinal tract is critical in food intake regulation. Signals from different levels of the digestive system are processed to the brain, among other systems, via the vagus nerve, which mainly projects towards the nucleus of the solitary tract (NST). The objective of this study was to analyze the participation of the gelatinous part (SolG) of the NST in short-term food intake. One-third of the stomach food content was withdrawn at 5 min after the end of a meal, and food was then available ad libitum for different time periods. SolG-lesioned and control animals ingested a similar amount of the initial liquid meal, but the former consumed significantly smaller amounts and failed to compensate for the food deficit, whereas the controls re-ingested virtually the same amount as extracted. These data suggest that the SolG, as in the case of related anatomical structures such as the vagus nerve or external lateral parabrachial subnucleus, may be relevant in particular circumstances that require the rapid processing of vagal-related food intake adjustment associated to the upper gastrointestinal tract.

Chemical afferent vagal axotomy blocks re-intake after partial withdrawal of gastric food contents.

OBJECTIVES: The aim of this study was to investigate the biological process by which animals regulate meal size. An experimental procedure for its study is to examine food re-intake after partial withdrawal of gastric food contents. METHODS: The aim of the present experiments was to investigate the role of vagal afferents in food re-intake after perivagal administration of capsaicin, a neurotoxin that specifically damages weakly myelinated or unmyelinated vagal sensory axons. RESULTS: In experiment 1, capsaicin-treated animals initially consumed higher amounts of food in comparison to controls (in first 24 hours) but their excess intake was compensated for in subsequent daily satiation tests. However, capsaicin treatment impaired the common short-term re-intake behavior observed in control rats after partial removal of gastric food nutrients, and the lesioned animals consumed significantly less food than had been withdrawn after completion of the initial meal; moreover, in this deficit condition, no counteraction was observed in subsequent repeated tests. This behavioral disturbance cannot be attributed to an indirect effect of capsaicin on gastric emptying volume, because the stomach contents were similar in both groups (Experiment 2). DISCUSSION: These findings are discussed in terms of the critical role played by vagal afferents in rapid visceral adjustments related to short-term food intake, as also observed in other gastrointestinal regulatory behaviors that require immediate processing of visceral sensory information.

Naloxone blocks the aversive effects of electrical stimulation of the parabrachial complex in a place discrimination task.

The parabrachial complex is known to participate in various rewarding and aversive processes, including those related to the learning of taste or place discrimination and the motivational effects of drugs of abuse, such as morphine. This study shows that electrical stimulation of the external lateral parabrachial (LPBe) subnucleus induces consistent place avoidance or place preference in three-compartment rectangular mazes. Administration of naloxone, an opiate antagonist, blocks both motivational effects induced by the intracranial electrical stimulation. Subsequent re-administration of the electrical stimulation was found to recover its aversive but not its rewarding effects after vehicle administration. These results are discussed in relation to different natural and artificial agents involved in the induction of avoidance and preference motivational processes, especially with regard to the opioid system.

Satiation and re-intake after partial withdrawal of gastric food contents: A dissociation effect in external lateral parabrachial lesioned rats.

Sensory information from the gastrointestinal system can be transmitted to the brain through the vagus nerve, the intermediate-caudal region of the nucleus of the solitary tract (NST), and various subnuclei of the parabrachial complex, notably the external lateral subnucleus (LPBe). The objective of the present study was to examine the relevance of this subnucleus in satiation and food reintake after gastrointestinal food removal. LPBe-lesioned animals were subjected to a re-intake task following the partial withdrawal of gastric food contents shortly after satiation. Lesioned and control animals ingested a similar amount of the initial liquid meal. However, after withdrawal of one-third of the food consumed, LPBe-lesioned rats were not able to compensate for the deficit created, and their re-intake of food was significantly lower than the amount withdrawn after the satiating meal. In contrast, the food re-intake of control animals was similar to the amount withdrawn. Hence, the LPBe does not appear to be critical in the satiation process under the present experimental conditions. However, the LPBe may be part of a system that is essential in rapid visceral adjustments related to short-term food intake, as also shown in other gastrointestinal regulatory behaviors that require immediate processing of visceral sensory information.

Tolerance to repeated rewarding electrical stimulation of the parabrachial complex.

The parabrachial complex has been related to various rewarding behavioral processes. As previously shown, electrical stimulation of the lateral parabrachial external (LPBe) subnucleus induces opiate-dependent concurrent place preference. In this study, two groups of animals (and their respective controls) were subjected to sessions of rewarding brain stimulation daily or on alternate days. The rats stimulated every other day maintained a consistent preference for the place associated with the brain stimulation. However, as also found in the Insular Cortex, there was a progressive decay in the initial place preference of animals receiving daily stimulation. These data suggest that the rewarding effects induced by electrical stimulation of LPBe subnucleus may be subject to tolerance. These findings are discussed with respect to other anatomical areas showing reward decay and to the reinforcing effects induced by various electrical and chemical rewarding agents.

Differential effects of naloxone on rewarding electrical stimulation of the central nucleus of the amygdala and parabrachial complex in a place preference study.

The central nucleus of the amygdala (CeA) is considered to be involved in different affective, sensory, regulatory, and acquisition processes. This study analyzed whether electrical stimulation of the PB-CeA system induces preferences in a concurrent place preference (cPP) task, as observed after stimulation of the parabrachial-insular cortex (PB-IC) axis. It also examined whether the rewarding effects are naloxone-dependent. The results show that electrical stimulation of the CeA and external lateral parabrachial subnucleus (LPBe) induces consistent preference behaviors in a cPP task. However, subcutaneous administration of an opiate antagonist (naloxone; 4mg/ml/kg) blocked the rewarding effect of the parabrachial stimulation but not that of the amygdala stimulation. These results are interpreted in the context of multiple brain reward systems that appear to differ both anatomically and neurochemically, notably with respect to the opiate system.

Animal models of Central Diabetes Insipidus: Human relevance of acquired beyond hereditary syndromes and the role of oxytocin.

The aim of this study was to review different animal models of Central Diabetes Insipidus, a neurobiological syndrome characterized by the excretion of copious amounts of diluted urine (polyuria), a consequent water intake (polydipsia), and a rise in the serum sodium concentration (hypernatremia). In rodents, Central Diabetes Insipidus can be caused by genetic disorders (Brattleboro rats) but also by various traumatic/surgical interventions, including neurohypophysectomy, pituitary stalk compression, hypophysectomy, and median eminence lesions. Regardless of its etiology, Central Diabetes Insipidus affects the neuroendocrine system that secretes arginine vasopressin, a neurohormone responsible for antidiuretic functions that acts trough the renal system. However, most Central Diabetes Insipidus models also show disorders in other neurobiological systems, specifically in the secretion of oxytocin, a neurohormone involved in body sodium excretion. Although the hydromineral behaviors shown by the different Central Diabetes Insipidus models have usually been considered as very similar, the present review highlights relevant differences with respect to these behaviors as a function of the individual neurobiological systems affected. Increased understanding of the relationship between the neuroendocrine systems involved and the associated hydromineral behaviors may allow appropriate action to be taken to correct these behavioral neuroendocrine deficits.

Naloxone impairs concurrent but not sequential flavor aversion: Resorting to a flexible/explicit learning.

The role of opiate systems has been extensively studied in relation to learning and memory. Naloxone (Nx), an opiate antagonist, was administrated in concurrent (Experiment 1) and sequential (Experiment 2) flavor aversion learning (FAL) tasks. The outcomes demonstrate that Nx impairs the acquisition of concurrent but not sequential FAL. In the concurrent learning (7 trials), both control (vehicle) and Nx2 (treated with Nx only on the first 2 days) groups learned the task. Furthermore, these 2 groups retained the learning in a discrimination test without drug administration (Day 8) but failed a reversal test (Day 9). In contrast, the Nx group (7 trials with Nx) showed no concurrent learning but correctly performed the discrimination test (Day 8) and, critically, the reversal test. These results suggest that Nx blocks concurrent (implicit) learning in these experiments but induces animals to resort to new strategies that are flexible, a characteristic of explicit learning.

Tolerance to repeated rewarding electrical stimulation of the insular cortex.

The insular cortex (IC) has been related to various reinforcing behavioral processes. This study examined the effect of electrical stimulation of the posterior agranular IC on concurrent place preferences. Two groups of animals and their respective controls underwent rewarding brain stimulation every day or on alternate days. While the rats stimulated every other day maintained their preference for the place associated with brain stimulation, those stimulated every day evidenced a reduction in their place preference, suggesting tolerance to the stimulation's rewarding effect. A 15% increase in the current intensity produced a recovery of the preferences of the daily-stimulated rats but had no effect on those stimulated on alternate days. These results are discussed in terms of the rewarding effects induced by different electrical and chemical rewarding agents.

Opposite effects of oxytocin on water intake induced by hypertonic NaCl or polyethylene glycol administration.

Oxytocin (OT), a neurohormone, has been related to natriuretic and diuretic effects and also to water intake and sodium appetite. The objective of the present study was to determine the effect of subcutaneous OT administration on water intake and urine-related measures induced by the administration of hypertonic NaCl (experiment 1) or polyethylene glycol (PEG) (experiment 2). Experiment 1 showed that OT administration increases the urine volume, urinary sodium concentration, and natriuresis and reduces the water intake, water and sodium balances, and estimated plasma sodium concentration induced by hypertonic NaCl administration. Conversely, experiment 2 showed that OT administration increases the water intake and the antidiuretic response induced by PEG administration. These results show that the opposite effects of OT on the water intake induced by hypertonic NaCl or PEG administration are accompanied by differential regulatory effects, enhancing a natriuretic response in the first experiment and generating an antidiuretic reaction in the second experiment. This study suggests a differential regulatory effect of OT during states of intra- and extracellular thirst.

Lesions of the central nucleus of the amygdala only impair flavor aversion learning in the absence of olfactory information.

The amygdala is considered a crucial brain nucleus in different modalities of aversive conditioning, including flavor aversion learning (FAL). The importance attributed to the amygdala and its subnuclei has frequently depended on the different stimuli and procedures used in FAL tasks. In this study, FAL was impaired only in animals that had lesions in the central nucleus of the amygdala (CeA) area and also had their olfactory bulbs removed. However, this task was learned by neurologically intact animals, bulbectomized animals, and rats with lesions exclusively centered in the CeA area alone. These results suggest that the CeA area may be relevant in gustatory-gut associative learning but not in FAL, in which the olfactory system may counteract the deficit produced in taste-visceral convergence.

Rewarding effects of electrical stimulation of the insular cortex: decayed effectiveness after repeated tests and subsequent increase in vertical behavioral activity and conditioned place aversion after naloxone administration.

The insular cortex has been associated with various aversive and rewarding sensory, regulatory, and learning processes. The objective of this study was to examine the characteristics of the reinforcement induced by electrical stimulation of this brain area in rats. Results obtained confirm that electrical stimulation of the insular cortex may induce conditioned place and flavor preferences but the learning acquired is not transferred in a reversal test. Unexpectedly, they also demonstrate that this rewarding effect diminishes after repeated tests. In follow-up experiments, locomotor activity tests revealed an increased number of rearings (a sensitization index) in stimulated animals. Furthermore, in these same animals, administration of low doses of naloxone, an opiate antagonist, developed place aversion toward the maze compartment for which the animals had previously shown preference. These results are interpreted in relation to the effects induced by the repeated administration of natural and artificial rewarding stimuli.