Reversal of dexfenfluramine-induced anorexia and c-Fos/c-Jun expression by lesion in the lateral parabrachial nucleus

The external subdivision of the lateral parabrachial nucleus (LPBE) shows strong Fos-like immunoreactivity (FLI) following anorectic doses of the indirect serotonin agonist dexfenfluramine (DFEN). In an effort to determine the contribution of the LPBE to DFEN-induced anorexia, bilateral ibotenate lesions were made in the LPBE, and the effects of the lesion on DFEN-induced anorexia and FLI as well as c-June-like immunoreactivity (JLI) were examined. It was found that LPBE lesion significantly attenuated DFEN anorexia: in a 1-h food intake test following 24-h food deprivation, DFEN (2 mg/kg) suppressed food intake by 60% in intact rats but only 34% in rats with LPBE lesions. In addition to this behavioral change, LPBE lesion completely abolished DFEN-induced FLI and JLI in the lateral subdivision of the central nucleus of the amygdala (CeL) and laterodorsal subdivision of the bed nucleus of stria terminalis (BSTLD), both of which showed strong FLI and JLI in intact rats. DFEN-induced FLI and JLI in other brain regions were not affected by LPBE lesion, including the ventromedial and lateral hypothalamus, caudate-putamen, and the nucleus of the solitary tract (NST). The parallel loss of DFEN-induced anorexia and FLI/JLI following LPBE lesion raises the novel possibility that LPBE-CeL/BSTLD pathway may be involved in DFEN anorexia.     

The role of the area postrema in the anorectic effects of amylin and salmon calcitonin: behavioral and neuronal phenotyping

Amylin reduces meal size by activating noradrenergic neurons in the area postrema (AP). Neurons in the AP also mediate the eating‐inhibitory effects of salmon calcitonin (sCT), a potent amylin agonist, but the phenotypes of the neurons mediating its effect are unknown. Here we investigated whether sCT activates similar neuronal populations to amylin, and if its anorectic properties also depend on AP function. Male rats underwent AP lesion (APX) or sham surgery. Meal patterns were analysed under ad libitum and post‐deprivation conditions. The importance of the AP in mediating the anorectic action of sCT was examined in feeding experiments of dose–response effects of sCT in APX vs. sham rats. The effect of sCT to induce Fos expression was compared between surgery groups, and relative to amylin. The phenotype of Fos‐expressing neurons in the brainstem was examined by testing for the co‐expression of dopamine beta hydroxylase (DBH) or tryptophan hydroxylase (TPH). By measuring the apposition of vesicular glutamate transporter‐2 (VGLUT2)‐positive boutons, potential glutamatergic input to amylin‐ and sCT‐activated AP neurons was compared. Similar to amylin, an intact AP was necessary for sCT to reduce eating. Further, co‐expression between Fos activation and DBH after amylin or sCT did not differ markedly, while co‐localization of Fos and TPH was minor. Approximately 95% of neurons expressing Fos and DBH after amylin or sCT treatment were closely apposed to VGLUT2‐positive boutons. Our study suggests that the hindbrain pathways engaged by amylin and sCT share many similarities, including the mediation by AP neurons.     

Medial versus lateral parabrachial nucleus lesions in the rat: effects on cholecystokinin- and D-fenfluramine-induced anorexia

The two major components of the pontine parabrachial nucleus (PBN), the medial (gustatory) and lateral (visceral) subdivisions, have been implicated in a variety of ingestive behaviors. The present study examined the influence of bilateral ibotenic acid lesions of the medial or lateral PBN on the anorectic effects of two systemically administered drug treatments. In Experiment 1, 24-h food-deprived rats where injected with sulfated cholecystokinin (26-33) (CCK; 0, 4.0, or 8.0 microg/kg) and then given 60 min access to food. In Experiment 2, the influence of D-fenfluramine (DFEN; 0, 0.5, 1.0, or 2.0 mg/kg) on deprivation-induced feeding was examined in the same rats using the same behavioral procedure as in Experiment 1. Lesions of the lateral PBN abolished CCK-, but not DFEN-induced anorexia whereas lesions of the medial PBN augmented DFEN-, but had no influence on CCK-induced anorexia. The results suggest that the satiating effects of CCK and DFEN are mediated through different mechanisms involving, respectively, visceral and orosensory processing.     

Medial versus lateral parabrachial nucleus lesions in the rat: effects on cholecystokinin- and -fenfluramine-induced anorexia

The two major components of the pontine parabrachial nucleus (PBN), the medial (gustatory) and lateral (visceral) subdivisions, have been implicated in a variety of ingestive behaviors. The present study examined the influence of bilateral ibotenic acid lesions of the medial or lateral PBN on the anorectic effects of two systemically administered drug treatments. In Experiment 1, 24-h food-deprived rats where injected with sulfated cholecystokinin_26-33 (CCK; 0, 4.0, or 8.0 μg/kg) and then given 60 min access to food. In Experiment 2, the influence of -fenfluramine (DFEN; 0, 0.5, 1.0, or 2.0 mg/kg) on deprivation-induced feeding was examined in the same rats using the same behavioral procedure as in Experiment 1. Lesions of the lateral PBN abolished CCK-, but not DFEN-induced anorexia whereas lesions of the medial PBN augmented DFEN-, but had no influence on CCK-induced anorexia. The results suggest that the satiating effects of CCK and DFEN are mediated through different mechanisms involving, respectively, visceral and orosensory processing.     

Decreased NPY innervation of the hypothalamic nuclei in rats with cancer anorexia

Whether the decrease in food intake that occurs at the onset of anorexia in tumor bearing (TB) rats is related to a change in the hypothalamic neuropeptide Y (NPY) system was tested by comparing NPY expression in sham operated Fischer Control and anorectic TB rats. Coronal cryocut sections of their fixed brain were processed by the peroxidase-antiperoxidase method with NPY polyclonal antibodies. NPY-immunoreactive fibers were widely distributed throughout the forebrain, but were most prominent in the hypothalamic paraventricular, suprachiasmatic, arcuate and periventricular nuclei. NPY-immunoreactive neurons were visualized in Control and anorectic TB rats in the preoptic region, the arcuate nucleus, and occasionally in the lateral hypothalamus. Semiquantitative image analysis showed a significant decrease in the NPY immunostaining in some hypothalamic nuclei of the anorectic TB rats, most prominently in the supraoptic nucleus, the parvocellular portion of the paraventricular nucleus, and, to a lesser extent, the suprachiasmatic and arcuate nuclei. No changes in NPY innervation were seen in the ventromedial nucleus and the lateral hypothalamus. The data support the hypothesis of an altered hypothalamic NPY system at the onset of anorexia in TB rats and also reveal the hypothalamic nuclei through which NPY influences food intake.     

Anorexia following the intrahypothalamic administration of amylin.

The intrahypothalamic injection of rat amylin reduced feeding in schedule-fed rats for eight hours. Specificity of this anorectic response was indicated by an appropriate dose-response relationship and the absence of effect of human amylin. Amylin-induced anorexia was accompanied by alterations in neurotransmitter metabolism similar to those observed in anorectic tumor-bearing rats. These results indicate that amylin may inhibit feeding by acting directly on hypothalamic neurons to alter metabolism of neurotransmitter systems known to affect feeding behavior.     

Fos expression by glutamatergic neurons of the solitary tract nucleus after phenylephrine-induced hypertension in rats

The baroreflex pathway might include a glutamatergic connection between the nucleus of the solitary tract (NTS) and a segment of the ventrolateral medulla (VLM) called the caudal ventrolateral medulla. The main goal of this study was to seek direct evidence for such a connection. Awake rats were subjected to phenylephrine- (PE-) induced hypertension (N=5) or received saline (N=5). Neuronal activation was gauged by the presence of Fos-immunoreactive (Fos-ir) nuclei. Fos-ir neurons that contained vesicular glutamate transporter 2 mRNA (glutamatergic neurons) or glutamic acid decarboxylase mRNA (GABAergic neurons) were mapped throughout the medulla oblongata. Saline-treated rats had very few Fos-ir neurons. In PE-treated rats, Fos-ir neurons were detected in both NTS and VLM. In NTS, 72% of Fos-ir neurons were glutamatergic and 26% were GABAergic. In the VLM, 41% of Fos-ir neurons were glutamatergic and 56% were GABAergic. In VLM, Fos-ir glutamatergic neurons were evenly distributed and were often catecholaminergic, whereas Fos-ir GABAergic cells were clustered around Bregma -13.0 mm. This region of the VLM was injected with Fluoro-Gold (FG) in eight rats, four of which received PE and the rest saline. Fos-ir NTS neurons retrogradely labeled with FG were detected only in PE-treated rats. These cells were exclusively glutamatergic and were concentrated within the NTS subnuclei that receive the densest inputs from arterial baroreceptors. In conclusion, PE, presumably via baroreceptor stimulation, induces Fos in glutamatergic and GABAergic neurons in both NTS and VLM. At least 29% of the Fos-ir glutamatergic neurons of NTS project to the vicinity of the VLM GABAergic interneurons that are presumed to mediate the sympathetic baroreflex.     

C-fos expression in the rat brain after intraperitoneal injection of lithium chloride.

The distribution of evoked expression of the proto-oncogene c-fos was immunohistochemically examined in the rat brain after intraperitoneal injection of isotonic LiCl, which is commonly used to induce internal malaise in the conditioned taste aversion paradigm. C-fos-like immunoreactive neurones (c-fos neurones) were most densely observed in the central amygdaloid nucleus, external lateral subnucleus of the parabrachial nucleus (PBN), posteromedial and commissural parts of the nucleus of the tractus solitarius (NTS) and area postrema (AP). Experiments including vagotomy, intravenous injection of LiCl and lesions of the area postrema suggest that NTS neurones are activated via both sides of the vagus nerves, while AP neurones, humorally as well as neurally via the vagal nerve with a right side predominance. The activated NTS and AP neurones project mainly to the external lateral subnucleus of the PBN and lightly to the central lateral subnucleus of the PBN. These results are discussed in terms of the role of LiCl in the formation of conditioned taste aversion.     

Fos-like immunoreactivity and thirst following hyperosmotic loading in rats with subdiaphragmatic vagotomy

If receptors in the gut relay information about increases in local osmolality to the brain via the vagus nerve, then vagotomy should diminish this signaling and reduce both thirst and brain Fos-like immunoreactivity (Fos-ir). Water intake in response to hypertonic saline (i.p. or i.g., 1 M NaCl, 1% BW; i.g., 0.6 M NaCl, 0.5% BW) was reduced during 120 min in rats with subdiaphragmatic vagotomy (VGX) compared to sham-VGX rats. Brain Fos-ir was examined in response to both i.g. loads. After the smaller load, VGX greatly reduced Fos-ir in the supraoptic nucleus (SON) and the magnocellular and parvocellular areas of the paraventricular nucleus (PVN). Fos-ir in the subfornical organ (SFO) and nucleus of the solitary tract (NTS) was not affected. After the larger load, VGX significantly reduced Fos-ir in the parvocellular PVN and in the NTS, but not in the other regions. Thus, decreased water intake by VGX rats was accompanied by decreased Fos-ir in the parvocellular PVN after the same treatments, indicating a role for the abdominal vagus in thirst in response to signaling from gut osmoreceptors. The decreased water intake in the VGX group was not reflected as a decrease in Fos-ir in the SFO. Absorption of the larger i.g. load may have activated Fos-ir through more rapidly increasing systemic osmolality, thereby obscuring a role for the vagus at this dose in the SON and magnocellular PVN.     

Medial parabrachial nucleus neurons modulate d-fenfluramine-induced anorexia through 5HT2C receptors

We previously reported that lesions of the medial parabrachial nucleus (PBN) enhanced d-fenfluramine (DFEN)-induced anorexia; a finding that suggests these lesions may potentiate the release of serotonin (5HT) or increase the postsynaptic action of 5HT. In the present study, we used SB 206553 (a 5HT2B/2C receptor antagonist) or m-CPP (a 5HT2C/1B receptor agonist) in a standard behavioral procedure (deprivation-induced feeding) to further explore the role of the medial PBN in drug-induced anorexia. In Experiment 1, DFEN (0 or 1.0 mg/kg) was given alone or in combination with SB 206553 (2.0 or 5.0 mg/kg). In Experiment 2, we investigated the food-suppressive effects of m-CPP (0.5, 1.0 or 2.0 mg/kg). The results of Experiment 1 show that SB 206553, while having no influence on the performance of control subjects, attenuated (2.0 mg/kg) or abolished (5 mg/kg) the potentiating effect of the lesions on DFEN-induced anorexia. In Experiment 2, m-CPP induced a suppression of food intake in nonlesioned animals that was significantly potentiated in rats with medial PBN lesions. These results are consistent with the hypothesis that medial PBN neurons mediate anorexia through 5HT2C receptors.     

Lesions of the dorsal vagal complex abolish increases in meal size induced by NMDA receptor blockade

Rats increase meal size and duration after intraperitoneal injection of MK-801, a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist. This effect depends upon intact vagal fibers, since the antagonist does not increase intake when visceral afferent and efferent pathways have been interrupted by bilateral subdiaphragmatic vagotomy. NMDA receptors have been demonstrated on vagal afferent fibers and on second-order neurons in the medial subnucleus of the solitary tract (NTS), the area postrema (AP), and the dorsal motor nucleus of the vagus. To determine whether neurons in these structures are crucial for NMDA receptor effects on feeding, we examined the effect of MK-801 on intake of 15% sucrose in rats with aspiration lesions of the AP and adjacent NTS. MK-801 (100 microg/kg, i.p.) significantly increased sucrose intake in these lesioned rats compared to sham-lesioned rats (32.3+/-0.1 ml versus 23.3+/-0.1 ml, P<0.001). However, when the AP/NTS aspiration lesions were combined with bilateral electrolytic destruction of the medial NTS and the DMV, lesioned rats consumed nearly the same amount of sucrose after either saline or MK-801 (25.9+/-2.4 ml versus 24.3+/-3. 0 ml; P=0.687). By contrast, sham-lesioned controls ingested significantly more sucrose following MK-801 compared to saline (19. 8+/-1.0 ml versus 13.1+/-0.8 ml, P<0.001). These results suggest that an intact caudomedial NTS and/or DMV are necessary for increases in intake induced by NMDA receptor blockade. While the AP might participate in MK-801-induced enhancement of intake, it is not essential for this effect.     

The area postrema lesions alter the inhibitory effects of peripherally infused pancreatic polypeptide on pancreatic secretion

Circulating PP binds to specific receptors in the DVC through the AP, but the mechanism through which these brain receptors affect pancreatic secretion is not clear. We hypothesize that the removal of the AP (APX) will alter the effects of PP on pancreatic secretion. APX or sham procedures were performed in anesthetized male Wistar rats. After a 1-month recovery, one group of rats were infused with either PP (30 or 100 pmol/kg per h) or vehicle under basal or 2-DG-stimulated (75 mg/kg, i.v. bolus) conditions for studying pancreatic exocrine secretion. A second parallel group was sacrificed for examination of PP receptor binding in the brain stem. A third group received an intraperitoneal injection of PP at the dose of 4.15x10(4) pmol/kg (200 microg/kg) and c-fos expression in the brain stem was examined. APX eliminated PP binding sites in the DVC as assessed by autoradiography. PP infusion caused a dose-dependent decrease in basal protein secretion. APX partially reversed PP inhibition of basal protein secretion when infused at 30 pmol/kg per h, and at 100 pmol/kg per h stimulated pancreatic fluid secretion and reversed the inhibition of protein secretion. During 2-DG stimulation the effects of PP and 2-DG on pancreatic fluid and protein secretion were parallel. PP dose-dependently inhibited 2-DG-stimulated secretion in sham rats. APX reduced the pancreatic fluid (54%) and protein (46%) secretory response to 2-DG. However, PP at 30 pmol/kg per h remained a potent inhibitor of 2-DG-stimulated pancreatic secretion in APX rats. This effect was blunted with PP at 100 pmol/kg per h in APX rats, possibly related to the stimulatory effect of high-dose PP in APX rats without 2-DG. Furthermore, i.p. PP induced significantly greater c-fos activation of NTS neurons in APX rats than sham rats, despite the apparent absence of PP binding sites in the DVC. We conclude that in awake rats, PP inhibits basal secretion, in part, through the AP. Furthermore, and unlike PYY, PP inhibits 2-DG-stimulated pancreatic secretion, and it does so through an AP-independent mechanism. The possibility that the mechanism may involve the DVC cannot be excluded since i.p. injection of PP activates c-fos expression in DVC neurons. Thus, PP and PYY may regulate different components of the pancreatic secretory control system through unique pathways.     

Recovery of function in the albino rat following either simultaneous or seriatim lesions of the caudate nucleus

This study examines acquisition of spatial alteration performance and of passive avoidance behavior following seriatim lesions of the caudate nucleus in mature albino rats. Bilateral destruction of the caudate in one surgical operation has been shown to produce animals with well defined behavioral impairments; thus, the application of the seriatim surgical paradigm provides a means of evaluating the potential of the caudate damaged brain for functional reorganization. Lesions of the caudate nucleus were created by electrocoagulation, either bilaterally at one operation or in two sequential unilateral stages with a 25 day interlesion interval. A sham operated group was also employed. Rats having one-stage caudate lesions were impaired on spatial alternation when compared with two-stage and sham operated animals. Rats with two-stage lesions were better on passive avoidance than subjects with one-stage lesions and sham operated controls. These latter differences could not be accounted for by shock threshold or water consumption differences. There were no differences in the extent of the lesions between the animals that were subjected to one- and two-stage operations. These findings indicate that significant functional differences are produced by one-stage versus two-stage lesions of the rat caudate nucleus.     

Lesions of the central nucleus of the amygdala decrease taste threshold for sodium chloride in rats

Previous studies reported that NaCl intake was down-regulated in rats with bilateral lesions of the central nucleus of the amygdala (CeA). In line with the evidence from anatomical and physiological studies, such an inhibition could be the result of altered taste threshold for NaCl, one of the important factors in assessing taste functions. To assess the effect of CeA on the taste threshold for NaCl, a conditioned taste aversion (CTA) to a suprathreshold concentration of NaCl (0.1M) in rats with bilateral lesions of CeA or sham lesions was first established. And then, two-bottle choice tests between water and a series of concentrations of NaCl were conducted. The taste threshold for NaCl is defined as the lowest concentration at which there is a reliable difference scores between conditioned and control subjects. Rats with CeA lesions acquired a taste aversion for 0.1M NaCl when it was paired with LiCl and still retained the aversion after the two-bottle choice test. The results of the two-bottle choice test showed that the taste threshold for NaCl was 0.0006M in rats with CeA lesions, whereas in rats with sham lesions the threshold was 0.005M, which was identical to that of normal rats. The conditioned results confirm the claim that CeA is not essential in the profile of conditioned taste aversion. Our findings demonstrate that lesions of the CeA increased the sensitivity to NaCl taste in rats, indicating that the CeA may be involved in encoding the intensity of salty gustation elicited by NaCl.     

The area postrema is involved in paraquat-induced conditioned aversion behavior and neuroendocrine activation of the hypothalamic-pituitary-adrenal axis

Paraquat is a herbicide capable of eliciting conditioned taste aversion (CTA), a behavioral response characteristic of toxicosis. The area postrema (AP) is a hindbrain circumventricular organ previously shown to be important in mediating signs of paraquat-induced toxicity, namely CTA and weight loss. The relationship between neural substrates for paraquat-induced CTA and activation of the hypothalamic-pituitary-adrenal (HPA) axis was investigated in Sprague-Dawley rats with lesions centered on the AP (APX) and sham-operated (SHM) rats administered paraquat (25 μmol/kg) or saline (1 ml/kg). Injection of paraquat at a dose sufficient to condition taste aversion, but produce no other signs of overt toxicity, significantly increased plasma corticosterone concentrations in SHM rats up to 4 h after administration. Paraquat-induced activation of the HPA axis was significantly attenuated in AP-lesioned rats as compared to sham-operated controls. These findings suggest the area postrema is a common neural substrate for the behavioral and neuroendocrine responses to paraquat.     

Cardiovascular and neuroendocrine responses to behavioral stress after central or peripheral barodenervation in rats

The cardiovascular and neuroendocrine responses to acute behavioral stress were evaluated in rats after disruption of the baro reflexes by electrolytic lesions of the nucleus tractus solitarii (NTS) or sinoaortic denervation (SAD). Rats with NTS lesions or SAD showed significantly greater increases in mean arterial pressure (MAP) and plasma norepinephrine (NE) concentrations than control rats during a single 30-min escape-avoidance test. In addition, the increases in MAP and plasma NE concentration of NTS lesion rats were significantly greater than those of SAD rats. However, NTS lesion raats showed no increase in plasma renin activity (PRA), as observed in the other groups. Thus, disruption of the baroreflexes by NTS lesions oraugments the arterial pressure and plasma NE responses to stress. Additionally, NTS lesions appeared to eliminate the neurons or fibers of passage participating in the sympathetically mediated increase in PRA.     

Effects of vagotomy on cholecystokinin- and dexfenfluramine-induced fos-like immunoreactivity in the rat brain

This study compared the effects of bilateral subdiaphragmatic vagotomy on the Fos-like immunoreactivity (FLI), a marker of neuronal activation, in rat brain induced by two anorectic agents, cholecystokinin (CCK) and the serotonin agonist, dexfenfluramine (DFEN). In the nonvagotomized rats, both CCK (5 μg/kg, IP) and DFEN (2 mg/kg, IP) Induced FU in the nucleus of the solitary tract (MST), the external subdivision of the lateral parabrachial nuclei (LPBE), the lateral subdivision of the central amygdeloid nucleus (CeL), and the bed nucleus of the stria terminallis (BST). However, subregional distribution of the FLI induced by the two agents was different in most of these regions. Additionally, the area postrema and the medial subdivision of the hypothalamic paraventricular nucleus were preferentially activated by CCK but not DFEN, while the caudate-putemen was activated by DFEM but not CCK. Bilateral subdiaphragmatic vagotomy completely abolished CCK-induced FLI in all the brain regions but did not attenuate DFEN-Induced FLI in any of these regions, including the NST. The results of the present study suggest that DFEN-activation of the NST-LPBE-CeL/BST neuraxis is not mediated by the vague nerve. On the other hand, and consistent with a variety of other data, activation of various parts of the brain by peripherally administered CCK depends on a vagal pathway. These data are discussed in relation to a previously proposed interaction between CCK and serotonin in mediating satiety.     

Activation of Nesfatin‐1‐Containing Neurones in the Hypothalamus and Brainstem by Peripheral Administration of Anorectic Hormones and Suppression of Feeding via Central Nesfatin‐1 in Rats

Peripheral anorectic hormones, such as glucagon‐like peptide (GLP)‐1, cholecystokinin (CCK)‐8 and leptin, suppress food intake. The newly‐identified anorectic neuropeptide, nesfatin‐1, is synthesised in both peripheral tissues and the central nervous system, particularly by various nuclei in the hypothalamus and brainstem. In the present study, we examined the effects of i.p. administration of GLP‐1 and CCK‐8 and co‐administrations of GLP‐1 and leptin at subthreshold doses as confirmed by measurement of food intake, on nesfatin‐1‐immunoreactive (‐IR) neurones in the hypothalamus and brainstem of rats by Fos immunohistochemistry. Intraperitoneal administration of GLP‐1 (100 μg/kg) caused significant increases in the number of nesfatin‐1‐IR neurones expressing Fos‐immunoreactivity in the supraoptic nucleus (SON), the area postrema (AP) and the nucleus tractus solitarii (NTS) but not in the paraventricular nucleus (PVN), the arcuate nucleus (ARC) or the lateral hypothalamic area (LHA). On the other hand, i.p. administration of CCK‐8 (50 μg/kg) resulted in marked increases in the number of nesfatin‐1‐IR neurones expressing Fos‐immunoreactivity in the SON, PVN, AP and NTS but not in the ARC or LHA. No differences in the percentage of nesfatin‐1‐IR neurones expressing Fos‐immunoreactivity in the nuclei of the hypothalamus and brainstem were observed between rats treated with saline, GLP‐1 (33 μg/kg) or leptin. However, co‐administration of GLP‐1 (33 μg/kg) and leptin resulted in significant increases in the number of nesfatin‐1‐IR neurones expressing Fos‐immunoreactivity in the AP and the NTS. Furthermore, decreased food intake induced by GLP‐1, CCK‐8 and leptin was attenuated significantly by pretreatment with i.c.v. administration of antisense nesfatin‐1. These results indicate that nesfatin‐1‐expressing neurones in the brainstem may play an important role in sensing peripheral levels of GLP‐1 and leptin in addition to CCK‐8, and also suppress food intake in rats.     

Central renin injections: effects on drinking and expression of immediate early genes

This study investigated the drinking response and the expression of Fos- and Egr-1-immunoreactivity (Fos-ir; Egr-1-ir) in the brain induced by endogenous angiotensin generated by intracerebroventricular (i.c.v.) injection of renin. Renin induced Fos-ir in the subfornical organ (SFO), median preoptic (MnPO), supraoptic and paraventricular nuclei (SON and PVN), area postrema (AP), nuclei of the solitary tract (NTS) and lateral parabrachial nuclei (LPBN). Renin-induced Egr-1-ir exhibited a similar pattern of distribution as that observed for Fos-ir. The dose of i.c.v. renin that induced expression of immediate early gene (IEG) product immunoreactivity also produced vigorous drinking. When renin-injected rats were pretreated with captopril, an angiotensin converting enzyme inhibitor, drinking was blocked. With the same captopril pretreatment, both Fos- and Egr-1-ir in the SFO, MnPO, SON, PVN, AP and LPBN were also significantly reduced.     

Nucleus of the solitary tract and flavor aversion learning: relevance in concurrent but not sequential behavioral test

Theories relating the nucleus of the solitary tract to taste aversion learning (TAL) have received their main support from immunohistochemical research. In the present study, a behavioral analysis was performed on the effect of lesions of the intermediate nucleus of the solitary tract (iNST) on concurrent and sequential flavor aversion learning tasks. Bilateral lesions of the iNST impaired concurrent flavor learning, in which animals must discriminate between two simultaneously presented flavors paired with intragastric administration of a noxious or innocuous substance, respectively. However, the same iNST lesions did not interrupt the development of sequential flavor aversion learning, in which each flavor is offered individually on consecutive alternate days. These results behaviorally confirm the relevance of the nucleus of the solitary tract in TAL and suggest a functional dissociation between the neural systems underlying concurrent and sequential flavor aversion learning.