Central gustatory lesions: I. Preference and taste reactivity tests.

Bilateral electrophysiologically guided lesions were placed in the nucleus of the solitary tract (NST), the parabrachial nucleus (PBN), and the ventral posteromedial thalamic nucleus (VPMpc) of rats, and 15-min intake and taste reactivity (TR) responses elicited by 3 concentrations each of sucrose, NaCl, HCl, and quinine (Q) HCl were subsequently measured. Compared with controls, NST lesions had no significant effects on intake, and rats with PBN lesions consumed significantly more QHCl, sucrose, NaCl, and HCl. Thalamic lesions decreased sucrose intake. Analysis of TR responses showed that the QHCl threshold for aversive responses increased after VPMpc, PBN, and NST lesions. Rats with NST or PBN lesions were unresponsive to increasing sucrose concentration. TR responses elicited by NaCl and HCl were similar across the groups.     

Dietary sodium deprivation reduces gustatory neural responses of the parabrachial nucleus in rats

Acute sodium depletion induced by furosemide reduces gustatory responses of parabrachial nucleus (PBN) neurons to 0.3-0.5M NaCl in rats. However, in the rat nucleus of the solitary tract (NST), where taste-responsive cells project to the PBN, acute sodium depletion and dietary sodium deprivation elicit different response profiles to lingual NaCl stimulation. To examine the effect of dietary sodium deprivation on the responses of PBN gustatory neurons, we observed the taste responses of the PBN neurons to the four taste qualities and serial concentrations of NaCl in 15-day dietary sodium-deprived and control rats. The results showed that sodium deprivation reduced the responses of PBN taste neurons to 0.1-1.0M NaCl, but not to other tastants. Based on the analyses classified by best-stimulus categories, the number of NaCl-best neurons decreased from 68% to 45% following dietary sodium deprivation, and the responses of the NaCl-best neurons to 0.03-1.0M NaCl were significantly inhibited. Multidimensional scaling illustrated that sodium deprivation increased the similarity of the response profiles of the NaCl-best neurons. These findings suggest that dietary sodium deprivation might modulate sodium intake via increasing aversive threshold for salt rather enhancing salt discrimination.     

Parabrachial lesions disrupt responses of rats to amino acid devoid diets, to protein-free diets, but not to high-protein diets

Normal rats "reduce" intake of diets that lack an essential amino acid (THR-DEV), are protein free (PO%), or contain a high proportion of protein (P75%). We tested the importance of the parabrachial nuclei (PBN) in signaling such adjustments of food intake by placing electrophysiologically guided lesions in these nuclei at points that responded to gustatory stimuli. When fed the THR-DEV diet, rats with PBN lesions (PBNx) decreased their food intake significantly less than the controls (78.5 vs. 44.4%). When put on a P0% diet, PBNx animals decreased their intake only 8% compared with 23% for our CONT group. When put on a P75% diet, however, both groups decreased their intake in an equivalent amount. These experiments show that the PBN is involved in the learned aversion to an amino acid devoid diet.     

Lesions of the area postrema and underlying solitary nucleus fail to attenuate the inhibition of feeding produced by systemic injections of cholecystokinin in Syrian hamsters

A large body of evidence indicates that the intestinal hormone cholecystokinin (CCK) may serve as a signal for satiety. The abdominal vagus has been shown to be important for the satiety response to exogenous, and by inference, endogenous, CCK in rats and hamsters. Thus, it appears that stimulation of CCK receptors on afferent fibers of the abdominal vagus activates a gut-brain pathway to signal satiety. The present study was undertaken to further trace this viscerosensory pathway by examining food intake after administration of one of two doses (2.0 and 8.0 micrograms/kg) of CCK-octapeptide to intact hamsters and to hamsters sustaining lesions of the area postrema (AP) and underlying nucleus of the solitary tract (NST), regions containing neurons postsynaptic to vagal afferent fibers. As lesions of the AP/NST result in many alterations in ingestive behaviour and body weight regulation in rats, various aspects of feeding and drinking behaviour (spontaneous food intake, body weight maintenance, and responsiveness to a palatable drinking solution and osmotic stimulation) were also examined in lesioned hamsters. Aside from producing transient hypophagia and weight loss immediately after surgery, AP/NST lesions had no effects on these various parameters of ingestive behaviour. The lack of lesion effects on these particular parameters may be explained on the basis that hamsters are generally unresponsive to many of the stimuli for feeding and drinking which purportedly act on the vagus and/or AP/NST. Hamsters with AP/NST lesions were as responsive to the two tested doses of CCK as intact animals.(ABSTRACT TRUNCATED AT 250 WORDS)     

Lateral hypothalamic lesions and fenfluramine increase thermogenesis in brown adipose tissue

The effects of treatment with fenfluramine or electrolytic lesions in the lateral hypothalamus (LH) on binding of guanosine 5-diphosphate (GDP) by mitochondria from brown adipose tissue have been compared in 4 experiments. In 2 experiments the lesions were lateral to the anterior hypothalamic nucleus and in the other two they were lateral to the ventromedial hypothalamic nucleus. Binding of GDP to mitochondria was significantly increased 18 hours after an electrolytic lesion in either LH site. d,1-Fenfluramine, 20 mg/kg, also increased GDP binding in both acute experiments. In the other 2 experiments GDP binding was measured 11 days after the LH lesion or after 11 daily injections of fenfluramine. When the chronic lesions were lateral to the VMN, there was a transient drop in food intake and body weight. With more anterior lesions, body weight remained significantly lower than in sham-operated rats although food intake returned slowly to control levels. Fenfluramine-treated rats had lower body weights in both chronic experiments even after food intake returned to normal. GDP-binding to mitochondria from interscapular brown adipose tissue was elevated in both of the chronically-treated fenfluramine groups but was only increased in the LH-lesioned rats whose body weight remained below normal.     

Activity in the hypothalamus, amygdala, and cortex generates bilateral and convergent modulation of pontine gustatory neurons

Evidence suggests that centrifugal modulation of brain stem gustatory cells might play a role in the elaboration of complex taste-guided behaviors like conditioned taste aversion and sodium appetite. We previously showed that activity in one forebrain area, the central nucleus of the amygdala (CeA), increased the chemical selectivity of taste cells in the parabrachial nucleus (PBN). The present study investigates how activity in 2 other similarly interconnected forebrain sites, the lateral hypothalamus (LH) and gustatory cortex (GC), might influence PBN gustatory processing in rats. The potential convergence of descending inputs from these sites, as well as the CeA, was also evaluated. After anesthesia (35 mg/kg Nembutal ip), 70 PBN gustatory neurons were tested before, during, and after electrical stimulation of these forebrain sites, while responding to 0.3 M sucrose, 0.1 M NaCl, 0.01 M citric acid, and 0.003 M QHCl. Although each forebrain site modulated taste-evoked responses, more PBN neurons were influenced by stimulation of the GC (67%) and CeA (73%) than of the LH (48%). Activation of cortex (71%) and amygdala (85%) most often produced inhibition, whereas inhibition and excitation occurred equally often during hypothalamic stimulation. Of the neurons tested for convergence (n = 60), 88% were influenced by > or =1 of the 3 sites. Twenty were modulated by stimulation at all 3 sites and another 17 by 2 of the 3 sites. The net effect of centrifugal modulation was to sharpen the across-stimulus response profiles of PBN cells, particular with regard to the NaCl- and citric acid-best cells.     

Effects of brain lesions on taste-potentiated odor aversion in rats

Rats failed to acquire aversions to odor stimulus, which was followed 30 min later by an unconditioned stimulus (US). However, when the odor stimulus was accompanied by a taste stimulus, they acquired odor aversions as well as taste aversions. In this phenomenon, referred to as a taste-potentiated odor aversion, lesions of the amygdala disrupted both taste and odor aversions, whereas lesions of the parvicellular part of ventroposteromedial thalamic nucleus (VPMpc) or insular cortex (IC) disrupted taste aversion but attenuated only odor aversion. These results suggest that both taste and odor stimuli are associated with US in the amygdala and that taste inputs delivered to the amygdala through the IC and/or VPMpc play an important role in potentiation of odor aversion. ((c) 2006 APA, all rights reserved).     

Effects of central amygdaloid nucleus lesions on ingestion, taste reactivity, exploration and taste aversion.

Central amygdaloid nucleus lesions in rats had no effect on recovery of preoperative body weight and food consumption levels. The brain damaged rats also recovered preoperative levels of water consumption as rapidly as control rats but then developed a mild but persistent hypodipsia. The experimental rats also drank less than control rats when food deprived and showed marginally reliable decreases in 0.1% quinine solution consumption and latency to consume a novel food. There was no detectable lesion effect on 0.1% saccharin solution consumption, exploration of a novel environment or formation of a learned taste aversion. It is suggested that the central amygdaloid nucleus has a role in mediating the relationship between food and water intake and in some taste mediated consummatory behavior.     

Subnuclear organization of parabrachial efferents to the thalamus,amygdala and lateral hypothalamus in C57BL/6J mice: a quantitative retrograde double labeling study

The present study investigated the subnuclear organization of collateralized efferent projection patterns from the mouse parabrachial nucleus (PbN), the second taste relay in rodents, to higher gustatory centers, including the ventroposteromedial nucleus of the thalamus (VPMpc), central nucleus of the amygdala (CeA) and lateral hypothalamus (LH). We made injections of the retrograde tracer red and green latex microspheres into the VMPpc and CeA (VPMpc–CeA group), VMPpc and LH (VPMpc–LH group) or CeA and LH (CeA–LH group, n=6 for each group). Injections into these areas preferentially resulted in retrograde labeling in the ipsilateral PbN in all groups. Cells projecting to the VPMpc, CeA, and LH were generally found in all subnuclei, but were differentially distributed. VPMpc-projecting cells predominated in gustatory-related subnuclei, CeA-projecting neurons predominated in the external lateral (el) subnucleus, and concentrated labeling was observed in the dorsal lateral subnucleus (dl) following LH injection. Double-labeled neurons were found for all groups, almost entirely ipsilaterally and primarily in the medial (m), waist area (wa), ventral lateral (vl) and el subnuclei. These results suggest that PbN neurons in different subdivisions have different projection and collateralization patterns to the VPMpc, CeA and LH. Functional implications of these projections are discussed with an emphasis on their roles in taste.     

Increased sucrose intake and corresponding c-Fos in amygdala and parabrachial nucleus of dietary obese rats

The intake-excitatory effects of caloric foods are mainly due to the palatable taste and the ensuing positive postingestive effects. Dietary obese individuals are inclined to overeat high caloric foods. However, it is still unclear whether the taste or postingestive reinforcement mainly contributes to the excessive intake by obese individuals. In the present study, we measured 10- or 120-min sucrose solution drunk by dietary obese rats and measured c-Fos expression following 120-min tests in the central nucleus of amygdala (CeA), a forebrain nucleus involved in the hedonic reward and craving, and the parabrachial nucleus (PBN), a taste relay area responsive to positive postingestive effects. Dietary obese rats, compared with those fed normal chow, ingested larger amounts of sucrose solution (0.25 M) in the 120-min test, but not in the 10-min test. In addition, significantly more sucrose-induced c-Fos positive cells were found in the CeA, but much less in the external lateral subnucleus of the PBN of dietary obese rats. Our results demonstrate that increased sucrose intake in dietary obese rats is mainly due to the alteration of postingestive effects. The differences in these postingestive effects in obesity may involve greater positive/excitatory signals in which the CeA may play a role, and less negative/inhibitory signals in which the el-PBN may be involved.     

Centrifugal inputs modulate taste aversion learning associated parabrachial neuronal activities

Our previous studies have demonstrated that gustatory neurons in the parabrachial nucleus (PBN) show altered responses after the acquisition of conditioned taste aversion (CTA) to NaCl. The present study was conducted 1) to examine centrifugal influences on the altered gustatory activity of CTA-trained rats, and 2) to evaluate the role of amiloride-sensitive (ASN) and -insensitive NaCl (AIN) best units in coding the taste of NaCl. Animals were separated into 2 groups: a CTA group that had acquired taste aversion to 0.1 M NaCl and a control group that underwent pseudoconditioning before the recording experiment. Single-neuron activity, in 2 separate series of experiments, was extracellularly recorded in anesthetized rats. In the stimulation studies, the effects of electrical stimulation of the gustatory cortex (GC) or the central nucleus of amygdala (CeA) were examined on firing of PBN taste units. CeA stimulation produced excitatory effect in significantly more neurons in the CTA group (n = 8) than in the control group (n = 1). Furthermore, ASN-best units in the CTA group showed larger responses to NaCl than similar units in the control group. In the decerebration experiment, there was no statistical difference among the taste responses between the 2 groups in any best-stimulus category. These results suggest that CTA conditioning uses an effective central amygdaloid input to modulate activity of gustatory neurons in the PBN. Data also substantiate that amiloride-sensitive components of NaCl-best neurons play a critical role in the recognition of distinctive taste of NaCl.     

The effects on feeding of galanin and M40 when injected into the nucleus of the solitary tract, the lateral parabrachial nucleus, and the third ventricle.

Several reports indicate that central injection of galanin stimulates feeding, and that there is macronutrient specificity in this response. In addition, the galanin receptor antagonist, M40, reduces food intake when injected centrally. The nucleus of the solitary tract (NTS) and the lateral parabrachial nucleus (PBN) contain galanin receptors, and are involved in the control of food intake. Hence, we sought to compare the feeding response to galanin injection into these areas with that of third ventricle (3V) galanin injection. The feeding response to injection of galanin was greatest for the 3V. Hindbrain injection of galanin stimulated food intake only at the beginning of the dark period. NTS injection of M40 inhibited intake of a macronutrient diet in food-deprived rats, but was ineffective at reducing dark-onset feeding or deprivation-induced chow intake. 3V injection of M40 did not reduce deprivation-induced intake. PBN injection of galanin at dark onset had no effect in a group of fat-preferring rats. These results suggest that hindbrain galanin may contribute to feeding by inhibiting satiety, and that hypothalamic galanin receptors are involved with stimulation of intake. Furthermore, the absence of a consistent pattern of the stimulation of macronutrient intake suggests that galanin may not be a significant effector of macronutrient selection during individual meals.     

Parabrachial gustatory lesions impair taste aversion learning in rats.

Lesions in the gustatory zone of the parabrachial nuclei (PBN) severely impair acquisition of a conditioned taste aversion (CTA) in rats. To test whether this deficit has a memorial basis, intact rats (n = 15) and rats with PBN lesions (PBNX; n = 10) received seven intraoral taste stimulus infusions (30 s, 0.5 ml) distributed over a 30.5-min period after either LiCl or NaCl injection. This task measures the rapid formation of a CTA and has minimum demands on memory. LiCl-injected intact rats progressively changed their oromotor response profile from one of ingestion to one of aversion. NaCl-injected intact rats did not change their ingestive pattern of responding. In contrast, there was no difference between LiCl- and NaCl-injected PBNX rats. These same PBNX rats failed to avoid licking the taste stimulus when tested in a different paradigm. A simple impairment in a memorial process is not likely the basis for the CTA deficit.     

Parabrachial nucleus lesions block taste and attenuate flavor preference and aversion conditioning in rats

Rats with ibotenic acid lesions of the parabrachial nucleus (PBN) failed to learn a taste aversion induced by lithium chloride (LiCl) toxicosis. The same rats also did not learn to prefer a taste that was paired with intragastric (IG) carbohydrate infusions during 22 hr/day trials. The PBN-lesioned rats did learn to prefer a flavor (odor + taste) paired with the IG carbohydrate infusions over a different flavor paired with IG water. The PBN-lesioned rats also learned to avoid a flavor paired with IG LiCl infusions during 22 hr/day trials. The flavor preference and aversion, however, were less pronounced than those displayed by control rats. These data indicate that the PBN is essential for forming orosensory-viscerosensory associations when taste is the primary cue but is less critical when more complex flavor cues are available.     

Response to chronic insulin administration: effect of area postrema ablation

The effects of daily administration of protamine zinc insulin (PZI) on plasma insulin and glucose levels and on food intake and body weight of rats with lesions of the area postrema and adjacent caudal-medial portions of the nucleus of the solitary tract (APX rats) were examined. Prior to insulin treatment, APX rats weighted less and had lower plasma immunoreactive insulin (IRI) levels than nonlesioned controls but did not differ from controls in plasma glucose levels. Five daily injections of 5 U/kg PZI raised plasma IRI and lowered plasma glucose levels similarly for both lesioned and nonlesioned rats. When injected with increasing doses of PZI over a 30-day period, both lesioned and nonlesioned rats showed increases of food intake and rate of weight gain in response to 8 U/kg PZI. These data indicate that APX does not affect either physiological or behavioral responses to chronic peripheral insulin administration.     

Patterns of increased and decreased ingestive behavior after injections of lithium chloride and 2-deoxy-D-glucose

In previous research, 750 mg/kg 2DG yielded a number of effects suggesting a postdrug nausea; and the present experiments revealed that the illness-inducing agent LiCl similarly produced taste aversion learning at 7.5 mg/kg, inhibited drinking in water-deprived animals at 30 mg/kg, depressed feeding in hungry rats at 60 mg/kg, and evoked food intake and pica at 120 mg/kg. The appearance of eating and pica at the same dosage suggested that rats may eat food as well as a nonnutritive substance as a species-specific reaction to illness and that postdrug feeding, including that observed after 2DG, is an insufficient condition for concluding that a treatment produces no internal distress. A liquid diet that reportedly ameliorates the glucoprivic feeding deficits produced by lateral hypothalamic and zona incerta lesions theoretically could produce its effects if lesions made rats more reactive to 2DG-induced malaise and if this diet were more palatable to animals experiencing internal distress. However, this liquid diet failed to facilitate food intake after LiCl, nor did it reduce the inhibited eating produced by LiCl in food-deprived subjects. Liquid diet effects in lesioned animals, therefore, may not be explained by factors related to a 2DG-induced malaise.     

Mercaptoacetate fails to block the feeding-inhibitory effect of the beta3-adrenergic receptor agonist CGP 12177A

Peripherally administered beta3-adrenergic receptor (beta3-AR) agonists stimulate lipolysis and inhibit food intake. To test the hypothesis that this inhibition of feeding is due to a substrate-driven increase in hepatic fatty acid oxidation (FAO), we assessed the ability of the FAO inhibitor mercaptoacetate (MA) to reverse the feeding-inhibitory effect of the beta3-AR agonist CGP 12177A (CGP). Adult male Sprague-Dawley rats received intraperitoneal injections of 1 mg/kg CGP, of 45.6 mg/kg MA, or of both drugs, and the effects on food intake, plasma free fatty acids (FFA), and plasma beta-hydroxybutyrate (BHB), an indicator for hepatic FAO, were assessed. Control rats received saline injections. CGP significantly reduced food intake after 0.5 and 6 h and increased plasma FFA and BHB at 0.5 h, suggesting increased lipolysis and hepatic FAO. MA completely reversed the increase in plasma BHB and thus appeared to effectively abolish CGP's effect on hepatic FAO, but MA failed to affect CGP's feeding-inhibitory action. These findings do not support the hypothesis that the beta3-AR agonist CGP inhibits feeding by enhancing hepatic FAO or ketogenesis. Although the beta3-AR agonist CGP reduced saccharin intake in a one-bottle condition taste aversion test, it seems unlikely that the hypophagic effect of CGP is elicited by malaise.     

PVN-hindbrain pathway involved in the hypothalamic hyperphagia-obesity syndrome

This study examined the involvement of caudal brainstem projections of the hypothalamic paraventricular nucleus (PVN) in the medial hypothalamic (MH) hyperphagia-obesity syndrome. Experiment 1 demonstrated that a unilateral parasagittal knife cut in the MH combined with a contralateral coronal knife cut in either the ventrolateral pons (vP) or ventrolateral medulla (vM) significantly increased food intake and body weight in adult female rats. Overeating and overweight were also produced by a unilateral MH knife cut combined with a contralateral oblique cut under the nucleus of the solitary tract and dorsal motor nucleus of the vagus complex (NST/DX). In contrast, an MH cut x dorsolateral medullary cut combination did not increase food intake or body weight compared to a MH cut alone or sham surgery. Experiment 2 demonstrated that the hyperphagia/obesity effect of MH x vP knife cuts was comparable to that obtained with bilateral PVN lesions, but less than that produced by bilateral MH knife cuts. Bilateral vP cuts also increased body weight but the effect was less than that obtained with the other experimental treatments. Feeding the rats a high-fat diet rather than chow potentiated the hyperphagia and obesity syndromes produced by the various lesion conditions. Taken together, these findings suggest that the medial hypothalamic hyperphagia and obesity syndrome is due, in part, to damage to PVN projections to the caudal brainstem, the NST/DX complex in particular. The functional significance of this PVN-hindbrain "feeding" pathway and the identity of extra-PVN components of the hyperphagia-obesity syndrome remain to be established.     

Effects of lesions of the ventral ventral median preoptic nucleus or subfornical organ on drinking and salt appetite after deoxycorticosterone acetate or yohimbine.

Lesions of the ventral ventral median preoptic nucleus (VVMnPO) enhanced daily salt appetite induced by subcutaneous (sc) injections of deoxycorticosterone acetate (DOCA) but did not affect acute salt appetite or water intake after sc injections of 5 mg/kg of the alpha-2-adrenoreceptor blocker yohimbine. Lesions of the subfornical organ (SFO) or its rostral fiber pathways had no effect on fluid intakes during DOCA treatments but significantly reduced water intake after yohimbine. These findings extend those of a previous report (Fitts, Tjepkes, & Bright, 1990) of enhanced DOCA-induced saline intake in VVMnPO-lesioned rats and demonstrate that the effect is specific to lesions of the VVMnPO. The mechanism of the thirst and salt intake elicited by yohimbine is still unclear, but the SFO and its fiber pathways appear to be important for the expression of the water drinking component. Neither lesion reliably affected yohimbine-induced salt appetite.     

Effects of amygdala lesions on body weight, conditioned taste aversion, and neophobia

Female rats with posterodorsal amygdala (PDA), basolateral amygdala (BLA), or sham lesions were compared regarding ad libitum food intake, weight gain, consumption of a novel food, and acquisition of a conditioned taste aversion (CTA). While only the rats with PDA lesions evidenced substantial weight gains at 10 days after surgery eating standard lab chow (25-45 g more than the other groups), only the rats with BLA lesions demonstrated significant deficits in the CTA and neophobia paradigms. Rats with basolateral lesions, on average, took less than 30 s to begin drinking the novel sweetened condensed milk after pairing with illness while the other groups took approximately 15 min to begin drinking. Also, rats with basolateral lesions ate, on average, 5 g of the novel Froot Loops while the other groups ate approximately 2 g. It is concluded that the changes in food-motivated behavioral tests frequently observed in animals with amygdala lesions do not coexist with the hyperphagia and weight gain of animals with PDA lesions.