Sodium Homeostasis, a Balance Necessary for Life.

Body sodium (Na) levels must be maintained within a narrow range for the correct functioning of the organism (Na homeostasis). Na disorders include not only elevated levels of this solute (hypernatremia), as in diabetes insipidus, but also reduced levels (hyponatremia), as in cerebral salt wasting syndrome. The balance in body Na levels therefore requires a delicate equilibrium to be maintained between the ingestion and excretion of Na. Salt (NaCl) intake is processed by receptors in the tongue and digestive system, which transmit the information to the nucleus of the solitary tract via a neural pathway (chorda tympani/vagus nerves) and to circumventricular organs, including the subfornical organ and area postrema, via a humoral pathway (blood/cerebrospinal fluid). Circuits are formed that stimulate or inhibit homeostatic Na intake involving participation of the parabrachial nucleus, pre-locus coeruleus, medial tuberomammillary nuclei, median eminence, paraventricular and supraoptic nuclei, and other structures with reward properties such as the bed nucleus of the stria terminalis, central amygdala, and ventral tegmental area. Finally, the kidney uses neural signals (e.g., renal sympathetic nerves) and vascular (e.g., renal perfusion pressure) and humoral (e.g., renin-angiotensin-aldosterone system, cardiac natriuretic peptides, antidiuretic hormone, and oxytocin) factors to promote Na excretion or retention and thereby maintain extracellular fluid volume. All these intake and excretion processes are modulated by chemical messengers, many of which (e.g., aldosterone, angiotensin II, and oxytocin) have effects that are coordinated at peripheral and central level to ensure Na homeostasis.

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.

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.

Changes in D1 but not D2 dopamine or mu-opioid receptor expression in limbic and motor structures after lateral hypothalamus electrical self-stimulation: A quantitative autoradiographic study.

Intracranial self-stimulation (ICSS) of the lateral hypothalamus (LH) is involved in the activation of neuroanatomical systems that are also associated with the processing of natural and other artificial rewarding stimuli. Specific components of this behavior (hedonic impact, learning, and motor behavior) may involve changes in different neurotransmitters, such as dopamine and opioids. In this study, quantitative autoradiography was used to examine changes in mu-opioid and D1/D2-dopamine receptor expression in various anatomical regions related to the motor and mesolimbic reward systems after intracranial self-stimulation of the LH. Results of the behavioral procedure and subsequent radiochemical assays show selective changes in D1 but not D2 or mu receptors in Accumbens-Shell, Ventral Pallidum, Caudate-Putamen, and Medial Globus Pallidus. These findings are discussed in relation to the different psychobiological components of the appetitive motivational system, identifying some dissociation among them, particularly with respect to the involvement of the D1-dopamine subsystem (but not D2 or mu receptors) in goal-directed behaviors.

Rewarding effects of the electrical stimulation of the parabrachial complex: taste or place preference?

The lateral parabrachial complex has been related to various emotional-affective processes. It has been shown that electrical stimulation of the external Lateral Parabrachial (LPBe) nucleus can induce reinforcing effects in place preference and taste discrimination tasks but does not appear to support self-stimulation. This study examined the relative relevance of place and taste stimuli after electrical stimulation of the LPBe nucleus. A learning discrimination task was conducted that simultaneously included both sensory indexes (taste and place) in order to determine the preference of animals for one or the other. After a taste stimulus reversal task, the rewarding effect of stimulation was found to be preferentially associated with place. These results are discussed in the context of the rewarding action and biological constraints induced by different natural and artificial reinforcing agents.

Conditioned place preference induced by electrical stimulation of the insular cortex: effects of naloxone.

The insular cortex has been related to various sensory, regulatory, and learning processes, which frequently include affective-emotional components. The objective of this study was to investigate the possibility of inducing reinforcing effects by electrical stimulation of this cortical region in Wistar rats. Concurrent conditioned place preference tasks were conducted for this purpose, using two rectangular mazes that differed in dimensions, texture, and spatial orientation. A significant correlation was found in the preferences induced by insular cortex electrical stimulation between the two mazes. Animals showed consistent preference or avoidance behaviors associated with simultaneous insular cortex stimulation. No electrical self-stimulation was achieved. In a second experiment, animals that showed consistent place preference after the simultaneous insular cortex electrical stimulation were administered with 4 mg/ml/kg of naloxone. The results revealed that this opiate antagonist blocked concurrent place preference learning when the task was conducted in a new maze but not when it was conducted in the same maze as that in which the animals had learned the task. These results are discussed in terms of the participation of the insular cortex in various reward and aversion modalities.

Concurrent stimulation-induced place preference in lateral hypothalamus and parabrachial complex: differential effects of naloxone.

Place preference induction by intracerebral electrical stimulation was initially shown by Olds and Milner. It has since proven possible to induce concurrent stimulation-induced place preference (cCPP) after electrical stimulation of the lateral hypothalamus (LH) and, more recently, of the external lateral parabrachial nucleus (LPBe). The objective of this experimental study was to examine whether the rewarding effects of electrical stimulation of the LH and LPBe involve the activation of similar opioid systems in an alternative cCPP task. Administration of the opioid antagonist naloxone (4mg/kg) blocked the conditioned place preference effect induced after LPBe but not after LH stimulation (at 4 or 10mg/kg). These results are interpreted in relation to the presence of multiple reward systems that might anatomically and neurochemically differ with respect to the involvement of the opioid system.

Conditioned place preference but not rewarding self-stimulation after electrical activation of the external lateral parabrachial nucleus.

The objective of this experiment was to examine the rewarding effect of electrical stimulation of the external lateral parabrachial nucleus (LPBe) and of the lateral hypothalamus (LH) in concurrent Conditioned Place Preference (cCPP) and Brain Self-Stimulation Rewarding tasks. As expected, LH-stimulated animals readily learned cCPP tasks and developed self-stimulation behaviours following the rate-frequency procedure. As previously demonstrated, stimulation of the parabrachial complex generated rewarding or aversive behaviours in cCPP procedures. However, stimulation of this subnucleus induced consistent cCPP behaviours but not brain self-stimulation in rewarding LPBe animals. These results are analysed in the context of the different natural and artificial rewarding effects found in the LPBe nucleus.

Consistent rewarding or aversive effects of the electrical stimulation of the lateral parabrachial complex.

Electrical stimulation of the external lateral parabrachial subnucleus (LPBe) may induce rewarding or aversive behaviors in animals subjected to two different learning discrimination tasks. Statistical analysis found no significant differences between the group receiving electrical stimulation of the brain and the non-stimulated control group. However, rewarding or aversive behaviors were consistent and positively correlated between the two discrimination tasks in the stimulated group. Thus, these tests differed in the gustatory stimuli used, in the right/left position of stimulation-associated/non-associated flavors, and in the cage in which experiments were performed. This behavioral consistency and corresponding correlation were not observed in the non-stimulated control group. These results suggest the existence of aversive and reward systems that are differentiated but anatomically very close. Therefore, the activation of aversive or rewarding systems may depend on the precise location of the electrode implanted in the LPBe of each animal.

Effects of intragastric administration of predigested nutrients on food intake, body weight and taste acceptability: potential relevance of the cephalic/neural phase of digestion.

In this study we analyzed the effect of the intragastric administration of partially digested and natural nutrients on subsequent food intake, body weight and flavor acceptability in rats. The results showed that enterally administered natural nutrients reduced the subsequent ingestion of food to a greater degree compared with the same nutrients in partially digested form. This greater reduction does not appear to be due to a higher nutritional effect of the former, because the body weight of both groups of animals was similar. Animals intragastrically administered with partially digested nutrients developed an acceptance response to a previously paired flavored stimulus, in contrast to animals receiving natural nutrients under the same conditions. These results are interpreted in terms of the cephalic phase of digestion and may be relevant to the treatment of clinical symptoms associated with enteral feeding.

Learned preferences induced by electrical stimulation of a food-related area of the parabrachial complex: effects of naloxone.

Electrical stimulation of the External Lateral Parabrachial Subnucleus (LPBe), a food-related area, induced behavioral preferences for associated stimuli in a taste discrimination learning task. Although this stimulation appeared to be ineffective to elicit standard lever press self-stimulation, it induced place preference for one of two training compartments of a rectangular maze in which animals (adult male Wistar rats) received concurrent electrical brain stimulation. In subjects that consistently showed a preference behavior in different trials, administration of the opioid antagonist naloxone (4 mg/ml/kg) blocked concurrent learning when the test was made in a new maze but not in the same maze in which animals had learned the task. These results are discussed in terms of the possible participation of the LPBe subnucleus in different natural and artificial brain reward systems.

Lesions of the lateral parabrachial area block the aversive component and induced-flavor preference for the delayed intragastric administration of nutrients in rats: effects on subsequent food and water intake.

The aim of this study was to examine the function of the lateral parabrachial area (LPB) in relation to the intragastric administration of nutrients. The consumption of flavors associated with intragastric nutrient administration and the subsequent food and water intake were measured in rats with lesions in the LPB. The results showed that bilateral LPB lesions prevented development of aversions and induced flavor preference when there was a delay between the presentation of a flavor and the intragastric administration of nutrients. However, these lesions did not disrupt development of the aversive process when there was no delay between the presentations. Likewise, the LPB lesions increased subsequent food intake when there was a delay but not when there was no delay between the presentations. In contrast, the water intake was reduced in both situations. These results are interpreted in terms of a dual visceral system for processing the intragastric effects of foods.