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.     

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.     

Medial versus lateral parabrachial nucleus lesions in the rat: effects on mercaptoacetate-induced feeding and conditioned taste aversion

The two experiments of the present study examined the influence of bilateral electrophysiologically-guided ibotenic acid lesions of the medial (gustatory) and lateral (viscerosensory) subdivisions of the parabrachial nucleus (PBN) on lipoprivic feeding and on the acquisition of a conditioned taste aversion. In Experiment 1, mercaptoacetate (0, 400, 600, or 800 micromol/kg) failed to enhance food intake in normal rats maintained and tested on standard laboratory chow. In the same procedure, rats with lesions of the medial or lateral PBN consumed less food during baseline but nonetheless were sensitive to the orexigenic action of mercaptoacetate. In Experiment 2, both types of PBN lesions prevented acquisition of a conditioned taste aversion induced by the oral self administration of lithium chloride. The results suggest that PBN neurons essential for conditioned taste aversion are not involved in the mercaptoacetate-induced feeding of rats maintained and tested on standard laboratory chow.     

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.     

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.     

Area postrema and the anorectic actions of dexfenfluramine and amylin

The present study examined whether the area postrema and adjacent nucleus of the solitary tract (AP/NTS) is necessary for the expression of anorexia to two classes of anorectic agent. The first agent is the serotonergic agonist, dexfenfluramine (DFEN) and the second is the pancreatic peptide, amylin. Rats were prepared with either aspiration lesions of the AP/NTS or a sham operation. Rats with such lesions (APX) displayed normal anorexia following administration of DFEN, but the anorectic effect of amylin was completely eliminated. The magnitude of a conditioned flavor aversion to DEN was similar in APX and sham operated controls but, unlike controls, APX rats did not reduce total intake in the two-bottle preference test. Finally, the induction of Fos-like immunoreactivity (Fos-ir) following either DFEN or amylin was examined in both APX and sham operated groups. Both agents induced Fos-ir in the AP and/or NTS of sham operated rats, and this region was entirely absent in the APX rats. DFEN-induced Fos-ir was reduced greatly in the PVN of APX rats, but appeared normal in several other regions surveyed, including the central nucleus of the amygdala and the dorsal striatum. In contrast, amylin-induced Fos-ir was reduced in many rostral brain regions of APX rats. These data indicate that neither the anorexia nor the flavor aversion that are produced by DFEN are dependent upon the AP, and in particular that Fos-ir induced by DFEN in the LPBE is not due to afferents from the AP/NTS. In contrast, the anorectic effect of amylin seems to be due principally to its direct action at the AP/NTS.     

Effects of lateral and medial septal lesions on exploratory behavior in the albino rat

The effects of selective medial and lateral septal lesions on exploratory behavior were studied in the rat. Three types of open-field test and two tests of object exploration were used. In the firts experiments, medial but not lateral septal lesions abolished exploration of an open-field accessible from the home-cage. No effects of either of the lesions were found in a standard open-field (Experiment 2). In the third experiment, rats with medial septal lesions were less active and showed a preference for the smaller compartments of the testing apparatus. These results suggest that a change in exploratory behavior following medial septal lesions may be primarily due to their effect on emotionality (increased fear). Two tests of object exploration (Experiments 4 and 5) showed that both types of selective septal lesions enhanced approaches to the novel object placed in the home-cage, but they did not affect object exploration and object preference in other conditions (Experiment 5). The same experiments revealed an increased level of activity (rearing and ambulation) in the rats with lateral septal lesions.It is concluded that the effect of medial septal lesions on exploration is due to increased fear of novel places (but not objects). Lateral septal lesions, on the other hand, increase activity in the rats but there is no evidence that this activity represents enhanced exploration.     

Localization of parabrachial nucleus neurons projecting to the thalamus or the amygdala in the cat using horseradish peroxidase.

Topographical localization of parabrachial nucleus (PBN) neurons projecting directly to the thalamus or the amygdala was examined in the cat by the horseradish peroxidase (HRP) method. After HRP injection in the central nucleus of the amygdala, PBN neurons labeled with the enzyme were seen ipsilaterally in the ventral portion of the lateral PBN as well as in the medial PBN. When the HRP injections were centered on the parvocellular portion of the posteromedial ventral nucleus of the thalamus (VPMpc), HRP-labeled neurons were observed ipsilaterally in the dorsal portion of the lateral PBN as well as in the medial PBN. Within the medial PBN, the distribution of neurons projecting to the amygdala overlapped that of neurons projecting to VPMpc; the cell bodies of the former neurons, however, tended to be more elongated than the latter, and the mean of the average soma diameters of the former was significantly larger than the latter. On the other hand, in the lateral PBN no significant differences were noted between the means of the average soma diameters of neurons projecting to VPMpc and those projecting to the amygdala. The PBN neurons in the cat were presumed to transmit gustatory and general visceral information ipsilaterally to the thalamic taste region and the limbic areas in the basal forebrain.     

The effects of delaying reward on choice preference in rats with hippocampal or selective septal lesions

Two experiments are reported in which rats were trained to choose one of two goal arms in a Y-maze, for water reward. In one arm, the rats always received water (the continuously reinforced-CRF-arm). In the other arm the rats only sometimes received water (the partially reinforced-PRF-arm). During the critical test phase in both experiments, we delayed the reward in the CRF arm only by 10 s. Experiment 1 tested intact rats given saline injections, or injections of chlordiazepoxide hydrochloride (Librium, 5 mg/kg), and rats with hippocampal or cortical control lesions. When reward was immediate in both arms all rats preferred the CRF arm. Once reward was delayed, the rats with hippocampal lesions switched their preference to the PRF arm, while the rats in the other treatment groups did not. Experiment 2 tested rats with medial septal lesions, lateral septal lesions or control operations in the same way. The rats with medial septal lesions, and to a lesser extent those with lateral septal lesions, switched their preference to the PRF arm when compared to the sham-operated controls. We conclude that damage to the hippocampus or its afferent pathway from the septum increases rats' sensitivity to temporal discontiguities between the outcome of a response and its emission.     

The parabrachial nucleus and conditioned taste aversion

The parabrachial nucleus (PBN) surrounds the brachium conjunctivum in the dorsolateral pons. Although composed of numerous subnuclei, the PBN is typically organized into medial and lateral subdivisions according to their location relative to the brachium. In rodents, the medial PBN is part of the central gustatory system, whereas the lateral PBN is a component of the visceral sensory system. Lesions of the PBN disrupt conditioned taste aversion, a critically important learning mechanism that prevents the repeated ingestion of toxic food. Relevant neurobehavioral literature is reviewed to elucidate the role of the PBN in taste aversion learning.     

Mapping study of the parabrachial taste-responsive area for the anterior tongue in the golden hamster

The locations of taste-responsive areas within the brainstem parabrachial nucleus (PBN), an obligatory taste relay in the golden hamster (Mesocricetus auratus), were mapped in relation to cytoarchitectural boundaries. The PBN was systematically searched for multiunit neural activity in response to a taste mixture composed of 0.1 M sucrose, 0.03 M NaCl, and 0.1 M KCl applied to the anterior tongue. Taste responses were located exclusively in one of three subdivisions of the medial PBN, which is thought to be specialized for gustatory processing, and in one of six subdivisions of the lateral PBN, which is thought to be specialized for general visceral processing. Based on Nissl-stained material, both the medial and lateral PBN subdivisions in the hamster were similar to those reported for the rat PBN. The largest group of taste-responsive cells encompassed two-thirds of the central medial subdivision, while a smaller group of taste cells was exclusively located within the ventral lateral subdivision. The two taste-responsive subdivisions are separated by the superior cerebellar peduncle and contain diverse cell types. The finding that anterior tongue taste may be exclusively represented in circumscribed cytoarchitecturally defined parts of two PBN divisions suggests that taste information from the anterior tongue is required for both specific gustatory and general visceral functions.     

Expression of c-fos protein in rat brain elicited by electrical stimulation of the pontine parabrachial nucleus.

The expression of Fos, the protein product of the primary response gene c-fos, was used metabolically to map the short-term (1 hr) effects of urethane and sodium pentobarbital anesthesia in rat. Subsequently, urethane-anesthetized rats were used to study the integrated response to electrical stimulation (1-1.5 hr) of the pontine parabrachial nucleus (PBN), an important center for relay of autonomic information in the brain. Immunohistochemistry was used to localize Fos-like immunoreactivity (FLI) in the brain. To approximate amounts of FLI in the conscious animal, rats were killed immediately after attaining surgical anesthesia with sodium pentobarbital (50 mg/kg) or urethane (1.2-1.7 gm/kg). No FLI was found in the brains of these rats. In rats killed 1 hr after anesthesia with sodium pentobarbital, FLI was found only in the habenulae. After 1 h of urethane anesthesia, low levels of FLI were found in the following areas: nucleus of the tractus solitarius (NTS); caudal and rostral ventrolateral medulla (VLM); lateral PBN; ventromedial, paraventricular, and supraoptic nuclei (SON) of the hypothalamus; medial preoptic area; central nucleus of the amygdala (ACE); endopiriform cortex; insular cortex; piriform cortex; and islands of Calleja. Electrical stimulation of the PBN (10 sec on, 10 sec off; 15-50 microA at 20 Hz for 60-90 min) in rats anesthetized with urethane led to increases in mean arterial pressure (10-30 mm Hg) and to ipsilateral increases of FLI in the lateral PBN, dorsal division of SON, ACE, endopiriform nucleus, insular cortex, piriform cortex, and islands of Calleja. In two animals, ipsilateral increases were found in the ventromedial hypothalamus and medial amygdaloid nucleus.(ABSTRACT TRUNCATED AT 250 WORDS)     

Lateral parabrachial nucleus lesions in the rat: aversive and appetitive gustatory conditioning

Previous research involving tests of innate preferences and aversions shows that bilateral ibotenic acid lesions of the visceral neurons located in the lateral parabrachial nucleus of the pons selectively disrupt consumption of those gustatory stimuli whose intake is augmented or restricted by their postoral consequences. The present study examined the performance of the same experimental subjects in learned preference and aversion tasks. The lesioned rats failed to develop a conditioned taste aversion (Experiment 1), a conditioned flavor preference (Experiment 2), and a conditioned aversion to the oral trigeminal stimulus, capsaicin (Experiment 3). The pattern of results from both types of taste-guided behaviors (innate and learned) suggests that excitotoxic lesions of the lateral parabrachial nucleus diminish sensitivity to gastrointestinal feedback which, in the present experiments, precludes aversive and appetitive associative learning.     

Involvement of the Bed Nucleus of the Stria Terminalis in Tonic Regulation of Paraventricular Hypothalamic CRH and AVP mRNA Expression

The bed nucleus of the stria terminalis (BNST) occupies a central position in pathways regulating hypothalamo-pituitary-adrenocortical (HPA) stress regulation. The potential role of the BNST in tonic neural control of HPA function was assessed by examining effects of selective BNST lesions on expression of ACTH secretagogues in HPA-integrative neurons of the medial parvocellular paraventricular nucleus. Anterior BNST lesions (ABN) involved major portions of the anteromedial, anterolateral, ventromedial, ventrolateral, dorsolateral and juxtacapsular subnuclei. These lesions resulted in significant (30%) decreases in corticotropin-releasing hormone (CRH) mRNA expression across the rostrocaudal extent of the medial parvocellular PVN, with no accompanying changes in basal arginine vasopressin (AVP) mRNA levels. Posterior BNST (PBN) lesions involved large but subtotal damage to the posterior intermediate, posterior medial, posterior lateral and preoptic subnuclei; these lesions resulted in small but significant changes in CRH mRNA and slight increases in number of AVP mRNA-producing parvocellular neurons. PBN effects on CRH mRNA expression were most pronounced at the caudal extent of the medial parvocellular zone, suggesting a topographic input from the posterior BNST to the PVN that is only partially compromised by PBN lesions. Analysis of individual cases revealed a correlation between damage of the anterolateral BNST and decreased CRH mRNA levels, and damage of the posterior intermediate and/or posterior medial BNST and increased CRH mRNA levels. The results suggest differential BNST input into HPA regulation, perhaps reflecting the diversity of limbic input into the BNST region.     

Projections of the parabrachial nucleus in the old world monkey

The efferent projections of the pontine parabrachial nucleus (PBN) were examined in the Old World monkey (Macaca fascicularis) using tritiated amino acid autoradiography and horseradish peroxidase histochemistry. Parabrachiofugal fibers ascended to the forebrain along three pathways: the central tegmental tract, the ventral ascending catecholaminergic pathway, and a pathway located on the midline between the medial longitudinal fasciculi. The PBN projected heavily to the central nucleus of the amygdala and the lateral division of the bed nucleus of the stria terminalis and moderately to the ventral tegmental area and the substantia nigra. Light terminal label also was present within the dorsomedial, ventromedial, lateral, supramammillary, and infundibular nuclei of the hypothalamus and the annular nucleus and the dorsal raphe nucleus within the brain stem. The overall pattern of terminal label was similar to that previously reported for nonprimate species, but several differences were notable. In monkey the projection to the ventrobasal thalamus did not coincide with the region that contains gustatory-responsive neurons. In rats, these parabrachiothalamic fibers convey gustatory activity but in the monkey these fibers may carry visceral afferent information. The projections from the PBN to the hypothalamus in the monkey were neither as widespread nor as intense as in the rat, and the monkey lacks a projection from the PBN to the frontal and insular cortices.     

Neural systems and the inhibitory modulation of agonistic behavior: a comparison of mammalian species

The olfactory bulb, lateral septum, medial accumbens, medial hypothalamus, dorsal and median raphe, and amygdala are known from experiments in rats to participate in the inhibitory modulation of defensiveness and predation but not social aggression. The present paper surveys the influence of these structures in the inhibitory control of these same dimensions of agonistic behavior in other species. The existing evidence suggests that lesions in the lateral septum, medial accumbens, medial hypothalamus, or the dorsal and median raphe (or PCPA-induced depletion or serotonin) induce hyperreactivity to the experimenter in mice, rats, cats, dogs, and humans in every instance where they have been tested with one exception. The exception is that lesions in the medial hypothalamus of mice do not induce heightened reactivity. The same lesions do not cause this dramatic increase in reactivity to the experimenter in gerbils, hamsters, guinea pigs, or rabbits but do heighten some other species typical patterns of defensiveness such as alarm calls and avoidance of contact with conspecifics. Lesions in these same areas in monkeys have not been observed to heighten defensive behaviors. Predatory killing or killing of young conspecifics has been observed in hamsters, mice, rats, and cats in every instance where they have been examined following lesions of the olfactory bulbs, lateral septum, medial accumbens, medial hypothalamus, or the dorsal and median raphe nuclei (or PCPA-induced depletion of serotonin). Social aggression has been decreased with these same lesions in each case where they have been examined except for septal lesions in hamsters which have been reported to heighten social aggression. Across species, the consistency with which lesions of the olfactory region, lateral septum, medial accumbens, medial hypothalamus, and dorsal and median raphe nuclei alter defensiveness and predation but not social aggression supports the inference that neural systems exist which subserve the inhibitory modulation of these dimensions of behavior. Finally, the evidence that the disruption of functioning within these structures in humans results in increased agonistic responses to environmental stimuli serves to further establish the important role of this neural circuitry in the normal inhibitory modulation of agonistic behavior in humans.     

Do forebrain structures compete for behavioral expression? Evidence from amphetamine-induced behavior, microdialysis, and caudate-accumbens lesions in medial frontal cortex damaged rats.

The neurochemical basis of behavioral changes following medial frontal cortex damage were investigated. Experiment 1 examined locomotion in response to D-amphetamine (1.5 and 5 mg/kg) in rats that had received bilateral aspirative lesions of the medial frontal cortex alone or in combination with 6-hydroxydopamine (6-OHDA) lesions of the nucleus accumbens or caudate-putamen. Relative to controls, medial frontal cortex rats were initially hypoactive (day 1 postoperative) but rapidly became hyperactive (days 5-15 postoperative). Locomotor-time profiles and stereotypy ratings showed that amphetamine produced a selective enhancement of locomotion at the expense of stereotyped behavior. Nucleus accumbens lesions blocked the locomotion but enhanced stereotyped behavior in the medial frontal cortex damaged rats, suggesting that amphetamine-enhanced locomotion is dependent upon the integrity of the nucleus accumbens. In Experiment 2, intracerebral microdialysis was used to examine whether alterations in dopamine (DA) or monoamine metabolites in the nucleus accumbens or caudate-putamen accompanied the lesion-induced changes in locomotion. There were no differences in extracellular DA or monoamine levels between control rats and medial frontal cortex rats when tested on day 1 or day 15 postsurgery, either when they were at rest, while they walked on a motor-driven belt, or after amphetamine treatment. Therefore, it seems unlikely that changes in amphetamine-induced locomotion following medial frontal cortex lesions are related to underlying modifications in dopaminergic activity in the nucleus accumbens. It is suggested that neural structures compete for behavioral expression and that postlesion behavioral alterations reveal the competitive advantage of remaining intact neural systems.     

Cytoarchitectonic Analysis of Fos-immunoreactivity in Brainstem Neurones Following Visceral Stimuli in Conscious Rats

Visceral inputs to the brain make their initial synapses within the nucleus of the solitary tract (NTS), where information is relayed to other brain regions. These inputs relate to markedly different physiological functions and provide a tool for investigating the topography of visceral processing in brainstem nuclei. Therefore, Fos immunoreactivity was used to determine whether a gastric stimulus affects neurones within different or similar parts of the NTS, ventrolateral medulla (VLM) and parabrachial nucleus (PBN), compared to a baroreceptive stimulus. The contribution of catecholaminergic neurones in these areas was studied by combining Fos and tyrosine hydroxylase (TH) immunoreactivity. Conscious male rats received either cholecystokinin (CCK) intraperitoneally to activate gastrointestinal afferents, or were made hypertensive by intravenous infusion of phenylephrine (PE) to activate baroreceptors. Tissue sections were processed immunocytochemically for Fos and/or TH. Phenylephrine infusion and CCK injection elicited Fos expression in distinct and in overlapping regions of the NTS and the VLM. Cholecystokinin injections increased the number of Fos-immunoreactive neurones in the area postrema (AP) and throughout the rostral-caudal extent of the NTS, including commissural neurones and the medial subnuclei. Some reactive neurones in NTS were also positive for TH, but most were not, and most of the TH-positive NTS neurones were not Fos-positive. In contrast, PE infusion produced a more restricted distribution of Fos-positive neurones in the NTS, with most neurones confined to a dorsolateral strip containing few TH-positive neurones. The medial NTS at the level of the AP and the AP itself were largely unresponsive, but rostral to the AP the medial NTS was labelled, including some TH-positive neurones. Both treatments produced labelling in the caudal and mid-VLM, but PE infusion had a stronger effect in the rostral VLM. In the PBN, CCK elevated Fos expression in several subregions, whereas PE infusion failed to specifically alter any subdivision. The results suggest that stimulation of baroreceptor and gastric afferents evoke both overlapping and cytoarchitectonically distinct pathways in the brainstem.     

The septo-hippocampal system and cognitive mapping

Rats were trained on a rewarded alternation task, run as a spatial working memory task on an elevated T-maze. Experiment 1 tested the effects of fornix-fimbria (FOFI) lesions on the acquisition, and of medial septal (MS) lesions on the acquisition and retention of this task, when the rats had to use information provided by being forced to run to a selected goal arm. The FOFI lesion produced an enduring impairment; the MS rats showed a severe impairment initially, but subsequently showed some behavioural recovery, when tested in acquisition or in retention. Experiment 2 similarly tested the effects of lateral septal (LS) lesions on acquisition of the task, and found an impairment which again showed signs of recovery with further testing. Experiment 3 was a transfer test conducted on the rats which had shown recovery in Experiments 1 and 2. The rats were now forced to use information provided by simply being placed on a selected goal arm. Both control animals and lesion animals showed identical choice accuracy, lower than that seen in Experiments 1 and 2. Experiment 4 tested acquisition of the task used in Experiment 3, and acquisition of a task in which the rat had to use information provided by running to the goal arm via a different route. Control rats again performed poorly, and scarcely differed from MS rats. It was concluded that rats have difficulty in using information about ‘places’, and that controls and lesion rats learn the tasks in the same way. The implications for ‘cognitive mapping’ hypotheses are discussed.     

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.