Electrical self-stimulation in the central amygdaloid nucleus after ibotenic acid lesion of the lateral hypothalamus.

This experiment was carried out in order to investigate the involvement of lateral hypothalamus (LH) in electrical self-stimulation of the central amygdaloid nucleus (CeA). Adult male Sprague-Dawley rats were bilaterally implanted with a guide cannula situated above each LH and with two electrodes in the CeA. Self-stimulation was subsequently obtained separately from both right and left electrodes. The LH was then lesioned unilaterally by ibotenic acid (IBO) injection. Eight days later, the effect of this unilateral lesion on self-stimulation of the ipsilateral and contralateral CeA was tested. Then the neurons of the remaining non-lesioned LH side were lesioned with IBO and self-stimulation was tested 15 days after the second lesion. Both unilateral as well as bilateral lesions of LH produced a significant decrease in CeA self-stimulation rates but had no significant effect on the reward effectiveness. The unilateral lesions did not produce any modification of the rate-intensity function in the contralateral CeA. This lesion-induced depression in performance was reversed by treatment with phenobarbital. These results provide clear evidence that the rewarding effects of CeA electrical stimulation do not result from the activation of the LH outputs and that the apparent decrease in CeA self-stimulation may result from the LH lesion-induced increase in the frequency of epileptiform manifestations that occur following amygdaloid stimulation.

Increase of the aversive value of taste stimuli following ibotenic acid lesion of the central amygdaloid nucleus in the rat.

Male Sprague-Dawley rats received bilateral ibotenic acid lesions of the central amygdaloid nucleus (CeA) and were compared to sham-lesioned rats in their response to different concentrations of saccharin and quinine solutions. In two-bottle choice test situation, the lesioned rats exhibited a lower saccharin preference at concentrations of 2.5; 7.5 and 25 mM, while their aversion towards quinine and the highest concentration of saccharin (50 mM) was increased. In a one-bottle test, the lesioned rats showed consistent decreases in their consumption of 2.5 and 7.5 mM saccharin solutions whereas their intake of 0.9 mM solution of saccharin was equal to that of the sham-lesioned rats. The lesion of the CeA had no significant effects on the acquisition of conditioned taste aversion. There was less postoperative weight gain in lesioned rats as compared to sham-lesioned animals but the lesion had no significant effect on daily water intake. These findings suggest that the CeA plays an important role in the normal response to exteroceptive food stimuli via modulation of the aversive value of taste stimuli. The results are discussed in the context of an interaction between the CeA and the lateral hypothalamus (LH) in the modulation of palatability and feeding behavior.

Alcohol consumption and gustatory hedonic profiles in Wistar-Kyoto hyper- and normoactive rat strains.

The purpose of the present study was to compare the consummatory behaviour of rats of the Wistar Kyoto Hyperactive (WKHA) strain, selected for their hyperactivity in a novel environment, with the normoactive Wistar-Kyoto (WKY) rats in three choice tasks: between water and increasing concentrations of saccharin, between water and increasing concentrations of quinine, and between water and a 10% (v/v) ethanol solution. The results of the present study show that: (1) WKHA rats exhibited a significantly higher acceptance of a 10% (v/v) alcohol solution than the normoactive control WKY rats when alcohol solution was the only available fluid; (2) WKHA rats also showed significantly larger alcohol intakes during the 15 days of choice between water and alcohol (WKY: 0.39 +/- 0.05; WKHA: 1.72 +/- 0.26 g/kg/day); (3) as frequently cited in the literature for other strains, the higher level of alcohol ingestion of WKHA rats was associated with a higher preference for saccharin; (4) no strain differences were observed in the water-quinine choice test. The discussion is mainly centred on the small alcohol consumption of the two strains, since the intake of WKHA rats is in the normal range for consumption of outbred strains, while the amount of alcohol consumption of WKY rats is very low and in the range of alcohol intake of non-preferring rat strains. It is concluded that the difference in alcohol consumption is mainly due to the low intake of the WKY rats and it is suggested that their different level of consumption might result from the particular behavioural profile of these rats.

Interaction between mu and kappa receptors located in the parabrachial area in the opioid control of preference threshold for saccharin: modulatory role of lateral hypothalamic neurones.

In the course of our previous analyses of gustatory reward processes, we showed that, in normal or sham-lesioned rats, the preference threshold for saccharin over water was observed with a 0.3mM solution of the sweetener. The same solution was neutral for rats whose lateral hypothalamic neurones had been destroyed by ibotenic acid. Furthermore, injection of small dose of morphine (50ng) in the second gustatory relay-station, the parabrachial area, suppressed preference for the 0.3mM saccharin solution in sham-lesioned rats, while the same injection induced preference in lesioned rats. The aim of the present study was to determine if this paradoxical effect of morphine, in particular the suppressive action observed in sham-lesioned rats, could be explained by a differential activation of µ and kappa receptors located in the parabrachial area. Using the choice test between 0.3mM solution of saccharin and water, we compared the effect of intra-parabrachial injection of 50ng of morphine to those obtained with the µ agonist DAGO, the putative endogenous kappa ligand, dynorphin A(1-13) (Dyn A(1-13)) and the kappa antagonist, nor-binaltorphimine (nor-BNI). Increasing doses of each agonist and the antagonist were tested in independent groups of rats including lesioned and sham-lesioned animals. The same doses of DAGO that increased preference in sham-lesioned animals, decreased saccharin and water intakes in lesioned rats. On the contrary, Dyn A(1-13) dose-dependently decreased preference in the control rats and increased preference in lesioned animals. The effects of increasing doses of nor-BNI were more variable. To clarify the respective roles of the µ and kappa receptors, we tested the effect of two mixtures: (1) the simultaneous injection of DAGO and Dyn A(1-13) at doses ineffective when tested separately reproduced the paradoxical effect of morphine in each group of rats; (2) morphine effects were reversed when kappa receptors were blocked by a prior injection of nor-BNI. Taken together, the results suggest that: (1) in the parabrachial area of the normal rat, two opioidergic components, behaving antagonistically to each other, are implicated in the control of gustatory preference, a µ component with rewarding properties and a kappa component with aversive properties; (2) the main effect of the lateral hypothalamic lesion is to invert the properties of these two components; and (3) at least in the parabrachial area, µ and kappa receptors are functionally coupled and must be co-activated to reproduce the full effect of morphine.

Gustatory preference-aversion profiles for saccharin, quinine and alcohol in Roman high- and low-avoidance lines.

Rats of the Roman high-(RHA) and low-avoidance (RLA) lines are known to differ in alcohol preference, since the RHA rats freely consume more ethanol than RLA animals. In order to investigate whether this difference in alcohol intake could be due to an alteration of the gustatory quality of ethanol induced by the selection, we compared taste preference and aversion responses of RHA and RLA rats in four procedures: saccharin-water choice; gustatory negative contrast; quinine-water choice and 10% v/v alcohol-water choice. Our results confirm that RHA rats drink more alcohol than RLA rats. In the saccharin-water choice task, RHA rats tended to show higher preference than RLA rats for the most palatable concentrations, while their aversion to the highest concentration of saccharin (50mM) was smaller than the aversion shown by RLA rats. The negative gustatory contrast test did not clearly differentiate the two lines, although only RHA rats showed significant negative contrast. Lastly, while RLA rats showed only aversion to quinine as the concentration increased, RHA rats did not show any aversion and preferred quinine to water at mid-range concentrations. To explain these results three hypotheses are briefly discussed: first, selective breeding for high avoidance learning could have enhanced brain reinforcement processes implicated in the evaluation of palatability. Secondly, selective breeding could have decreased aversiveness to quinine-adulterated solutions, as well as to saccharin and alcohol solutions which include a quinine-like taste component. Lastly, the present results suggest that the RHA rats may be high sensation-seekers whereas RLA animals are low sensation-seekers.

Cellular organization of lateral hypothalamic efferents to the central amygdaloid nucleus of the rat.

The present study aimed to describe the localization, organization and density of lateral hypothalamic neurones projecting to the central amygdaloid nucleus (CeA) using WGA-apoHRP-Au as a retrograde tracer. In the lateral hypothalamus (LH) a cluster of labelled neurones was located in the middle and posterior parts of this region. This retrograde labelling is organized into perifornical and juxtacapsular subpopulations. These results provide a neuroanatomical basis for the concept that these lateral hypothalamic neurones modulate projections from CeA to pons and brainstem autonomic and gustatory centres which integrate responses related to fundamental and adaptive behaviours, and could be related to self-stimulation behaviour elicited from the CeA.

Effects of morphine injection into the parabrachial area on saccharin preference: modulation by lateral hypothalamic neurons.

The aim of the present study was to analyze the effects of morphine injected into the second relay station of the gustatory input pathways, the parabrachial area, on preference for saccharin over water. This study was carried out using both rats whose lateral hypothalamic neurons had been lesioned by ibotenic acid and sham-lesioned rats. As already shown, an 0.3 mM solution of the sweetener, which was clearly preferred over water by the sham-lesioned animals, was neutral for the lesioned rats. The injection of 50 ng of morphine into each parabrachial area transformed this neutral response of the lesioned rats to a clear preference for the sweetener, whereas the preference of sham-lesioned rats for the same solution was converted to an aversive response. Likewise, with a more palatable solution of saccharin (2.5 mM), the injection of 50 ng of morphine decreased the preference of the nonlesioned rats but increased the preference of the lesioned animals. Using the 2.5 mM solution of saccharin, the intraparabrachial injection of higher doses of morphine (100 and 500 ng) did not greatly modify the preference for the sweetener but induced a significant decrease in total fluid intake that was still observed 11 h after the injection of the opiate. These results are discussed: the morphine-induced aversion observed in the nonlesioned rats could be explained either by a specific influence on certain opioid receptors in the parabrachial area or, more probably, by the stimulation of pathways involved in taste or visceral aversive processes and relaying in the parabrachial area.(ABSTRACT TRUNCATED AT 250 WORDS)

Hypothalamic melanin-concentrating hormone and alpha-neoendorphin-immunoreactive neurons project to the medial part of the rat parabrachial area.

Neurons in the middle and posterior parts of the lateral hypothalamus project to the parabrachial area, and in particular to the gustatory relay-station located in the medial part of this area. In the present study we have examined some of the neuropeptide immunoreactivities of the lateral hypothalamus neurons that project to the gustatory region of the parabrachial area. By coupling retrograde transport and immunohistochemistry, we found that 50-60% of medial parabrachial area-projecting cells located in the juxta-capsular region of the posterior lateral hypothalamus are labeled by rat melanin-concentrating hormone antiserum, while 28% of the retrogradely labeled neurons located in the perifornical lateral hypothalamus are visualized with alpha-neoendorphin antiserum. Moreover, a large number of terminals distributed throughout the parabrachial nucleus are immunoreactive to melanin-concentrating hormone or alpha-neoendorphin antisera. These immunoreactivities are not co-localized within the same lateral hypothalamic neurons. The potential role of these peptidergic projections in the reward mechanisms elicited in the medial parabrachial area and in the control of palatability is discussed.

Ibotenic acid lesion of the hypothalamic paraventricular nucleus produces weight gain but modifies neither preference nor aversion for saccharin.

We showed recently that bilateral ibotenic acid lesions of the lateral hypothalamus (LH) produced three main behavioral disturbances in the rat, i.e., an increase in the gustatory preference and aversion thresholds for saccharin, permanent body weight and water intake deficits, and an alteration of morphine-induced modulation of taste. The two first results could suggest that the modification of the gustatory thresholds and the ingestive deficits are closely interrelated. Given this situation, we hypothesized that, conversely, a brain lesion known to induce obesity and hyperdipsia would therefore decrease the gustatory preference and aversion thresholds for saccharin. In order to test this hypothesis we analyzed the effects of the bilateral lesion of the hypothalamic paraventricular nucleus (PVH) by injection of ibotenic acid (2 micrograms in each side) on saccharin preference. The main results are as follows: 1) The neurotoxin selectively destroyed parvicellular neurons while the magnocellular cells were spared. 2) In comparison to the normal daily gain in body weight of the sham-lesioned animals, the lesioned rats showed an enhanced weight gain that became significant from the third day after the surgery up until the day of sacrifice, 37 days later. 3) In contrast to electrolytic lesions of the PVH, the ibotenic acid lesions of this nucleus did not induce hyperdipsia. 4) Preference and aversion thresholds for saccharin were not significantly modified by the lesion. 5) Whereas low doses of morphine suppressed the preference for saccharin in sham-lesioned rats when the concentration of the sweetener solution was at the threshold value, this suppressive effect was not observed in PVH-lesioned rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Relationship of Met-enkephalin-like immunoreactivity to vagal afferents and motor dendrites in the nucleus of the solitary tract: a light and electron microscopic dual labeling study.

Methionine (Met5)-enkephalin has been implicated in autonomic functions involving vagal reflexes within the nucleus of the solitary tract (NTS). We examined the light and electron microscopic relationships between neurons containing methionine (Met5)-enkephalin-like immunoreactivity (MELI) and vagal afferents and motor dendrites in the rat NTS. A polyclonal antibody raised against Met5-enkephalin and showing maximal cross-reactivity with this peptide was localized by immunoautoradiography. In the same sections, vagal afferents and motor neurons were identified by histochemical detection of anterogradely and retrogradely transported horseradish peroxidase (HRP). By light microscopy, the MELI was detected in perikarya distributed principally in the dorsomedial, intermediate and parasolitary subdivisions of the NTS. These subnuclei as well as medial and commissural divisions of the NTS also showed: (1) aggregates of silver grains thought to overlie terminals containing MELI, and (2) anterogradely transported HRP in varicose processes. Electron microscopic analysis of the dorsomedial NTS at the level of the area postrema established that MELI was detectable in perikarya, dendrites, and axon terminals. Most of the MELI was associated with large dense core vesicles (dcvs). These opioid terminals formed primarily symmetric synapses on proximal and asymmetric synapses on distal dendrites. Analysis of the dendritic targets of terminals containing MELI revealed that 13/222 were in synaptic contact with dendrites also containing MELI. The remainder of the terminals containing MELI either lacked recognized junctions or formed synapses with unlabeled dendrites. In comparison to the terminals containing MELI in the same series of sections, anterogradely labeled vagal terminals extensively formed asymmetric junctions with distal dendrites and spines. Of the observed anterogradely labeled terminals 6/84 formed synapses with dendrites containing MELI and 3/84 with dendrites containing retrogradely transported HRP. The remainder of the junctions were with dendrites lacking detectable immunoautoradiographic or HRP-labeling. The majority of the recognized synapses on labeled dendrites were at more proximal sites possibly reflecting more limited detection of both MELI and retrogradely transported HRP in smaller dendrites. However, the presence of even a few junctions at proximal sites on dendrites where synaptic transmission is known to be more effective suggests a potentially strong modulation of both opioid and vagal motor neurons by visceral afferents in the NTS. In addition to forming synapses on dendrites, both vagal afferents and terminals containing MELI showed frequent synaptic associations with unlabeled terminals, but not with each other. This finding suggests that the previously demonstrated opiate binding sites on vagal afferents is most likely attributed to other endogenous opiates.

Modulation of saccharin preference by morphine and naloxone: inversion of drug effects as a function of saccharin concentration.

The aim of the present study was to verify and extend a recent, isolated observation showing that, in rats, a moderate dose of morphine may induce either an increase or a decrease in preference for saccharin, the direction of the response depending apparently on the concentration of the sweetener. Two experiments were performed successively. First, we showed that the preference threshold for saccharin (0.3 mM, two-bottle procedure) of rats placed on a schedule of restricted water access was significantly decreased following injection of 1 mg/kg of morphine. In the second experiment, three groups of naive rats were submitted to the preference test but the concentration of saccharin solution was different for each group, namely 0.3, 1 and 1.7 mM. After stabilization of the baseline responses the effect of morphine (1 mg/kg) was tested in each of the 3 groups. As observed previously morphine decreased the preference of the rats tested with the 0.3 mM solution, but markedly increased the preference of the two other groups tested with the 1 and 1.7 mM solutions respectively. The effects of low doses of naloxone (0.01, 0.1 and 1 mg/kg) were then tested on the same groups of rats with the same saccharin concentrations. The 0.01 mg/kg dose of the antagonist increased the preference for the groups of rats tested with the 0.3 and 1 mM solutions. The other two doses of naloxone decreased saccharin intake whatever the saccharin concentration used. It is suggested that these apparently paradoxical effects of morphine and naloxone could result either from the stimulation of opioid autoreceptors or from the differential stimulation of different opioid receptor subtypes.

Facilitation of learning consecutive to electrical stimulation of the locus coeruleus: cognitive alteration or stress-reduction?

This chapter summarizes behavioral and neurochemical data on the delayed effect of locus coeruleus stimulation on learning capabilities in the rat. The initial observation showed that electrical stimulation of the locus coeruleus of a 15-day-old-rat improved the early stages of acquisition and extinction of a food-reinforced task performed 4 weeks later. Neurochemical lesion of the dorsal noradrenergic bundle performed 10 days before the stimulation did not attenuate the behavioral effect, whereas the lesion of the locus coeruleus proper suppressed the subsequent behavioral improvement. More recently we showed that the increase of adrenocorticotrophin release consecutive to a moderate stressful situation was significantly lower in previously stimulated rats than in implanted non-stimulated animals. Furthermore, we demonstrated that the neurochemical lesion of the locus coeruleus increased neophobia in the open-field as well as in a specific exploration task. Taken together these data strongly suggest that the long-term improvement in acquisition and extinction of locus coeruleus-stimulated rats results mainly from an attenuated stress reaction when these animals are confronted with a new environment (beginning of acquisition) or a new situation (beginning of extinction). Finally, we were interested in investigating the possibility of some long-term neurochemical modifications that could be related to the observed behavioral effects. The most significant modification observed concerned certain subpopulations of adrenoceptors in specific brain regions. By using specific ligands of the beta-, alpha 1- and alpha 2-adrenoceptors, we studied the long-term effect (4 weeks) of the locus coeruleus stimulation on the kinetic characteristics of these three sub-types of receptors in four brain areas (the cortex, hippocampus, hypothalamus and brainstem). No significant alteration in the density of beta binding sites was observed in any of the four structures analyzed; likewise locus coeruleus stimulation did not modify the density or affinity of the beta-, alpha 1- and alpha 2-receptors in the brainstem. The density of alpha 1- and alpha 2-receptors was significantly increased in the cortex whereas in the hippocampus only the density of the alpha 2-receptors was increased. Finally, a very large increase of the density of alpha 2-adrenoceptors was observed in the hypothalamus (113%). In each case the increase in receptor density was also associated with a decreased affinity. A behavioral counterpart of these changes in the kinetic properties of the alpha 2-receptors has been observed by using a pharmacological approach.(ABSTRACT TRUNCATED AT 400 WORDS)

Ibotenic acid lesion of the lateral hypothalamus increases preference and aversion thresholds for saccharin and alters the morphine modulation of taste.

In a previous study we showed that bilateral ibotenic acid lesions of the lateral hypothalamus in rats induced an increase in gustatory preference thresholds for saccharin solutions and which were associated with body weight and daily water intake impairments. The first aim of the present study was an attempt to dissociate the body weight and water intake deficits from the increase in gustatory thresholds. For this purpose we compared the effect of simultaneous bilateral lesions of the lateral hypothalamus with the effect of successive lesions in which each unilateral destruction was separated by a 10-day interval. Rats injected with vehicle only (either simultaneously or successively) served as controls. The two types of lesion produced very similar deficits, namely permanent body weight and water intake decreases, as well as a shift to the right in gustatory preference-aversion functions for saccharin (two-bottle procedure). The second aim of the present study was to analyse the effect of morphine (2 mg/kg SC) on saccharin preference in both lesioned and control rats. It was observed that for moderate and high concentrations of the sweetener morphine increased preference for saccharin over water but this effect was similar in both groups of rats. However, with a low concentration of the sweetener (0.3 mM) morphine clearly induced an opposite effect in the two groups of rats: the significant preference for this concentration shown by the control rats after vehicle injection was converted to a neutral response, whereas the neutral response of the lesioned animals after vehicle injection was transformed by morphine to a significant preference for saccharin over water.(ABSTRACT TRUNCATED AT 250 WORDS)

Localization of lateral hypothalamic neurons projecting to the medial part of the parabrachial area of the rat.

We recently showed that electrical self-stimulation registered in the medial part of the parabrachial area, as well as the preference-aversion threshold to saccharin solutions were both significantly altered following ibotenic acid lesion of the lateral hypothalamic neurons. In order to identify the location of the neurons in the lateral hypothalamus directly projecting to the parabrachial area, we injected in the medial part of this area the retrograde tracer wheat germ agglutinin-inactive horseradish peroxidase coupled to colloidal gold. In the lateral hypothalamus a large number of labeled cells was constantly observed. This cluster of cells was located in the middle and posterior parts of the lateral hypothalamic area between the frontal plane corresponding to the posterior third of the ventromedial hypothalamic nucleus and the plane corresponding to the premammillary nuclei. In contrast, the anterior part of the lateral hypothalamus was unlabeled. Since the labeled neurons are located in the same region as those destroyed by our ibotenic acid lesions, the present results strongly suggest that these descending projections, originating in the posterior lateral hypothalamus, are implicated in reward mechanisms elicited from the parabrachial area.

Opposite effects of ibotenic acid and 6-hydroxydopamine lesions of the lateral hypothalamus on intracranial self-stimulation and stimulation-induced locomotion.

The purpose of the present study was to test the respective roles of the intrinsic neurons and of the catecholaminergic fibers in two behaviors elicited by electrical stimulation of the lateral hypothalamus, intracranial self-stimulation and the increase in locomotor activity produced by noncontingent stimulation. One group of rats was unilaterally injected in the middle lateral hypothalamus with a dose of ibotenic acid known to significantly decrease self-stimulation (4 micrograms/0.5 microliter). Two other groups received, in the same area, an injection of a small dose of 6-hydroxydopamine (2 micrograms/0.5 microliter). The rats of one of these groups were pre-treated with desmethylimipramine. Two other groups of rats were respectively injected with the vehicle of each neurotoxin. Eight days later all rats were bilaterally implanted with stimulation electrodes, one in the lesioned area, the other in the contralateral region. Each electrode of each animal was tested first for self-stimulation, then for locomotor activation measured in the open field produced by non-contingent stimulation. Whatever the lesion or the behavior tested, the response of the lateral hypothalamus contralateral to the lesioned area was normal. Self-stimulation was disturbed only with stimulation of the lateral hypothalamus lesioned by ibotenic acid. Self-stimulation in the lateral hypothalamus lesioned by 6-hydroxydopamine was normal. However, a significant loss of noradrenaline in the hippocampus and of dopamine in the striatum was observed. Furthermore, the brains of two rats unilaterally injected with the usual dose of 6-hydroxydopamine were processed for tyrosine hydroxylase immunocytochemistry.(ABSTRACT TRUNCATED AT 250 WORDS)

Neurochemical lesion of the nucleus locus coeruleus increases neophobia in a specific exploration task but does not modify endocrine response to moderate stress.

In order to test more specifically the role of the nucleus locus coeruleus (LC) in reaction to novelty, rats with bilateral 6-hydroxydopamine lesions of this nucleus, vehicle injected rats and non-operated animals were tested in the open-field and in the Hughes apparatus where motor activity is recorded in both a familiar and a non-familiar environment. In the open-field, the LC lesioned animals were significantly less active. A similar decrease of locomotor activity was observed in the Hughes test: the number of passages between the two boxes of the LC lesioned rats was significantly decreased. Likewise when the locomotor activities in the two boxes were pooled, the activity of the rats with lesions was significantly lower than the activity of the control rats, but in this case the locomotor deficit appeared only in the familiar box, the locomotor activity in the novel enclosure being the same in both LC lesioned and control animals. This result suggests that exploratory induced locomotion is not disturbed by the locus coeruleus lesion. The significant locomotor deficit showed by the LC lesioned rats in the familiar box could be due to an increased immobility induced by the stressful situation. Moreover, the deficit observed was the same whether the behavioral test began 4 days or 4 weeks after the lesion. Finally, at the end of the experiment, all rats were submitted to a moderate novel environmental stress and blood samples collected to measure the plasma levels of different stress hormones (ACTH, glucocorticoids, PRL, catecholamines).(ABSTRACT TRUNCATED AT 250 WORDS)

Gustatory preference-aversion thresholds are increased by ibotenic acid lesion of the lateral hypothalamus in the rat.

The main purpose of this study was to quantitate possible changes in the rewarding and aversive values of certain gustatory stimuli produced by bilateral ibotenic acid lesions of the lateral hypothalamus in the rat. Non-operated rats served as controls. Thirteen days after the operation, rats were placed on a water-deprivation schedule during 5 consecutive days. Rats were then given the choice of one of 5 concentrations of saccharin solution, using a two-bottle procedure. Fluid intake across concentrations generated a preference-aversion curve. The same type of procedure was used to obtain the aversion curve for increasing concentrations of quinine solution. The lesioned rats as well as the control animals showed a clear preference-aversion response to saccharin solutions and an aversive response to quinine solutions. However, the highest preference score of the lesioned rats was obtained with a saccharin concentration 3 times higher than the concentration preferred by the control rats. Moreover, unlike control rats operated animals did not show aversion to the highest concentrations of saccharin solutions. Finally in the lesioned rats the aversion threshold to quinine solutions was obtained with concentration 5 times higher than the concentration inducing aversion in the control rats. At the end of these experiments, rats used as controls were submitted, in turn, to bilateral lesion of the lateral hypothalamus. The change in the preference-aversion threshold of these rats in the saccharin choice procedure was the same as that observed with naive rats. Taken together, these results suggest that in the normal rat the palatability of certain gustatory stimuli is modulated by the intrinsic neurons of the lateral hypothalamus.

Electrical self-stimulation in the parabrachial area is depressed after ibotenic acid lesion of the lateral hypothalamus.

The involvement of lateral hypothalamic intrinsic neurons on electrical self-stimulation of the parabrachial area was analyzed. Rats were bilaterally implanted in the parabrachial area and with a guide cannula located above each lateral hypothalamus. They were subsequently tested for intracranial self-stimulation. Then, the lateral hypothalamus on one side of the brain was injected with ibotenic acid. The effect of the induced lesion was tested 8 days later on self-stimulation of the ipsilateral and contralateral parabrachial areas. The intrinsic neurons of the non-lesioned lateral hypothalamus were then destroyed with ibotenic acid. Self-stimulation was then tested 8, 12 and 30 days later. The unilateral lesion produced a significant decrease of self-stimulation using the electrode ipsilateral to the lesion, without any modification of the stimulation using the contralateral electrode. After bilateral lesion, self-stimulation was greatly reduced bilaterally. The results suggest that the main effect of the lesion was to increase the self-stimulation threshold. Given that the parabrachial area is a relay station for the gustatory inputs and that the intrinsic neurons of the lateral hypothalamus project back to the parabrachial area, the present results are tentatively interpreted as an indication that self-stimulation in this pontine area results from the activation of feedback loops between the lateral hypothalamus and the parabrachial area.

Clonidine-induced sedation is not modified by single or combined neurochemical lesions of the locus coeruleus, the median and dorsal raphe nuclei.

Single or combined neurochemical lesions of the locus coeruleus, the dorsal and the median raphe nuclei were performed on different groups of rats. Starting 10 days after the lesion, the locomotor activity of all rats was measured for 5 min every day in an open-field. For the first 21 days all lesioned rats, independently of the lesion site, were significantly less active than controls, but from the 11th to the 16th day the locomotor activity of lesioned animals increased progressively and, thus on days 15 and 16, the mean activity of all lesioned groups was not significantly different from that of the controls. From the 17th day onwards the sedative effect of small doses of clonidine (5-100 micrograms/kg) was measured. Neither single nor combined lesions modified the response to clonidine and the linear decrease of activity produced by increasing doses of clonidine was the same in all groups, lesioned or not. Biochemical assays showed a marked loss of corresponding amines as a result of the lesions in cortex, hippocampus and the brainstem. These results suggest that the alpha 2-receptors involved in clonidine-induced sedation are located neither on noradrenergic fibers coming from the locus coeruleus, nor on serotoninergic fibers originating in the median and dorsal raphe nuclei.

The role of intrinsic neurons in lateral hypothalamic self-stimulation.

In this brief review, we summarize some of our recent work concerning the effect of a specific lesion of the intrinsic neurons located in the middle part of the lateral hypothalamus on electrical self-stimulation of this structure by electrodes implanted along the medial forebrain bundle. In a first experiment the neurons of the lateral hypothalamus were destroyed unilaterally by local injection of ibotenic acid (4 micrograms in 0.5 microliter). The contralateral side served as the sham-lesion control. Between 10 and 20 days later, electrodes were bilaterally implanted, one in the lesioned area, the other in the contralateral hypothalamus. Intracranial self-stimulation (ICSS) was obtained separately for each electrode, at various current intensities, using a nose-poke response. ICSS from electrodes implanted in the lesioned area was decreased in all cases, whereas ICSS of the sham-lesioned side was normal. In a second experiment, two groups of rats lesioned and implanted as above, received two additional electrodes either in the anterior hypothalamus or in the posterior hypothalamus. In rats with electrodes in the anterior hypothalamus, the lesion produced a large deficit in self-stimulation when stimulation was applied to the anterior electrode ipsilateral to the lesion. Only 3 of 6 rats showed a decrease in ICSS with stimulation of the posterior hypothalamic electrode ipsilateral to the lesion. These results suggest that ICSS in the anterior part of the medial forebrain bundle is sustained by long fibers originating in the middle part of the lateral hypothalamus, while ICSS in the posterior part of the lateral hypothalamus may not depend on the neurons located in the lesioned area.