Search PubMed⌕ Search

Biomedical subjects

B Cardo

Publications and source records attributed to B Cardo.

At least 19 recordsLinked to original sources
PubMed1991

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)

Animals↗
PubMed1987

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.

Animals↗
PubMed1987

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.

Animals↗
PubMed1986

Delayed up-regulation of alpha-adrenoceptor populations in particular regions of the rat brain after stimulation of the nucleus locus coeruleus.

We previously showed that electrical stimulation of the nucleus locus coeruleus resulted 4 weeks later in greatly improved performance in the acquisition and extinction of a food-reinforced operant task. To ascertain whether adrenergic receptors of particular brain regions were involved in this long term behavioral modification, we studied the characteristics of alpha 1, and alpha 2 and beta-binding sites after stimulation of the locus coeruleus. In the first experiment these characteristics were studied, 4 weeks after treatment, in cortex, hippocampus, hypothalamus and the brainstem. Neither the number, nor the affinity of beta-receptors ([125I]iodocyanopindolol binding sites) was modified in any brain region. A significant increase in the number of alpha 1-receptors ([3H]prazosin binding sites) was observed in the cortex (62%). The number of alpha 2-receptors, ([3H]yohimbine binding sites), was significantly increased in cortex (99%), hippocampus (33%) and hypothalamus (113%). No significant alteration of the alpha 1, alpha 2 and beta-adrenoceptors was observed in the brainstem. To investigate the time course of these adrenoceptor changes, the characteristics of alpha 1, alpha 2 and beta-adrenoceptors were studied 2 weeks after stimulation using the same ligands and in the same brain regions. The only significant modifications observed were an increase of the alpha 2-adrenoceptors in the cortex (19.4%) and in the hypothalamus (54%). Furthermore, in both experiments, the increase in the number of alpha 1 and alpha 2-receptors was associated with a significant decrease in affinity. These results are discussed in relation to our previous behavioral and pharmacological findings.

Animals↗
PubMed1985

Comparison of deficits in electrical self-stimulation after ibotenic acid lesion of the lateral hypothalamus and the medial prefrontal cortex.

The aim of the present study was to compare the self-stimulation deficit produced by a unilateral injection of the neurotoxin, ibotenic acid, in the lateral hypothalamus (LH) to the deficit produced by the same unilateral injection in the medial prefrontal cortex (MPC). Four groups of adult male Sprague-Dawley rats were used: in two control groups, electrodes were bilaterally implanted in the LH (5 rats) or in the MPC (6 rats) and self-stimulation (ICSS) was obtained separately with the right and left electrodes. In the two experimental groups the intrinsic neurons of the LH (8 rats) or of the MPC (10 rats) were destroyed unilaterally by local injection of ibotenic acid (4 micrograms in 0.5 microliter); the other side served as the sham-lesioned control. Ten days later ICSS electrodes were implanted bilaterally, one in the lesioned area, the other in the contralateral region. As in the case of the control rats, ICSS was determined separately for each electrode, first by a rate dependent test (nose-poke) then by a 'rate-free' test (shuttle-box). In the LH and MPC control rats, ICSS responses were the same with stimulation on either side. In the LH-lesioned rats, the ICSS rates measured with the nose-poke test were significantly decreased with stimulation on the lesioned side, whereas rates with stimulation of the non-lesioned LH were normal. Likewise, while shuttle responses with stimulation of the non-lesioned LH were normal, the OFF-time was increased and the ON-time was decreased with stimulation of the lesioned LH. In the MPC-lesioned rats, ICSS (nose-poke) was totally suppressed and the shuttle responses were disorganized since neither the ON- nor the OFF-times changed in response to increasing current intensities. Nose-poke responses with stimulation of the non-lesioned MPC were just about normal. These results show that in the two brain regions studied local neurons are involved in ICSS. The difference in the magnitude of the deficit observed suggests, that the neuronal circuits involved in MPC self-stimulation are poorly represented whereas in the LH many neuronal circuits involved in these mechanisms overlap.

Animals↗
PubMed1985

Electrical self-stimulation deficits in the anterior and posterior parts of the medial forebrain bundle after ibotenic acid lesion of the middle lateral hypothalamus.

The aim of the present study was to analyse the involvement of the intrinsic neurons located in the middle lateral hypothalamus in electrical self-stimulation measured with electrodes in the anterior and posterior parts of the medial forebrain bundle. In rats without hypothalamic lesions, self-stimulation rates from both anterior and posterior electrodes were similar on either side of the brain. For all rats with ibotenic acid-induced lesions in the lateral hypothalamus, self-stimulation rates were lower with electrodes in the area of the lesion, while self-stimulation on the contralateral side was normal. In rats with electrodes in the anterior hypothalamus, the lesion produced a large deficit when stimulation was applied to the anterior electrode ipsilateral to the lesion. Only three rats showed a decrease in self-stimulation with stimulation of the posterior hypothalamic electrode ipsilateral to the lesion; self-stimulation of the other three rats was normal. These results suggest that self-stimulation in the anterior part of the medial forebrain bundle is supported by long fibers originating in the middle part of the lateral hypothalamus, while self-stimulation in the posterior part of the lateral hypothalamus can be influenced by another system not involved in reward processes observed in the rostral part of the medial forebrain bundle.

Animals↗
PubMed1983

Neurochemical lesion of the locus coeruleus of the rat does not suppress the sedative effect of clonidine.

The locus coeruleus of male rats was destroyed bilaterally by injection of 6-hydroxydopamine. Rats injected with the vehicle and normal rats served as controls. Starting 20 days after the lesion, the locomotor activity of all rats was measured for 5 min every day. For the first 6 days, the lesioned rats were significantly less active than control rats; from the 7th to the 15th day, on the other hand, the locomotor activity of the two groups of rats was the same. From the 16th day onwards, the sedative effect of small doses of clonidine (2.5-100 micrograms/kg) was measured in lesioned and control animals. In spite of an almost total loss of noradrenaline in the cerebral cortex and hippocampus and a 33% loss of noradrenaline in the brain-stem of the lesioned rats, the sedative effect of clonidine was the same as in the control rats. This result suggests that the sedation produced by clonidine is not dependent on presynaptically located alpha 2-adrenoceptors.

Animals↗
PubMed1983

Intrinsic neurons are involved in lateral hypothalamic self-stimulation.

The recent technique of using ibotenic acid to lesion selectively local neurons while sparing fibers of passage permitted us to answer a long-standing question: is lateral hypothalamic self-stimulation supported by fibers of passage or are the intrinsic hypothalamic neurons involved? Three groups of adult male Sprague-Dawley rats were used. In a normal group, electrodes were bilaterally implanted in the lateral hypothalamus and self-stimulation (ICSS) was obtained separately with the right and left electrodes, at various current intensities, using a nose-poke response. In the experimental group, the intrinsic neurons of the lateral hypothalamus were destroyed unilaterally by local injection of ibotenic acid (4 or 6 micrograms in 0.5 microliter); the other side served as the sham-lesion control. Ten days later ICSS electrodes were implanted bilaterally, one in the lesioned area, the other in the contralateral hypothalamus. As in the case of the normal animals, the rate of nose-poking (ICSS) was then determined separately for each electrode. In the normal rats, ICSS rates were the same with stimulation on either side and the increase in ICSS rate as a function of the increase in current intensity was the same on each side. In the experimental rats, ICSS of the lesioned side was decreased in all cases; moreover, after lesion with the 6 micrograms dose, ICSS was totally suppressed. Self-stimulation of the sham-lesioned side was not significantly different from that observed in the normal rats. In 6 rats sampled from the lesioned groups as well as in 3 additional unimplanted animals, biochemical assays compared dopamine and serotonin contents of the two striata and noradrenaline and serotonin contents of the two hippocampi. No difference was observed for these two structures between the side ipsilateral to the lesion and the contralateral side. Moreover, none of these monoamine levels differed from those seen in the unimplanted rats. These results, taken together, suggest that intrinsic lateral hypothalamic neurons are involved in ICSS.

Animals↗
PubMed1983

Enhancement of learning four weeks after stimulation of the nucleus locus coeruleus in the rat: differential effects of dorsal noradrenergic bundle lesion and lesion of the locus coeruleus proper.

In previous studies we showed that electrical stimulation of the nucleus locus coeruleus produced, four weeks later, a significant improvement in performance in acquisition of food-reinforced operant conditioning. In the two experiments reported here, we tested the role of the dorsal noradrenergic bundle and of the locus coeruleus proper in this long-term effect. Lesioning the dorsal noradrenergic bundle did not have a clear and consistent effect, whereas lesion of the nucleus coeruleus proper suppressed almost totally the beneficial effect of the stimulation. In the first experiment, the dorsal noradrenergic bundle was lesioned by local bilateral injection of 6-hydroxydopamine, 8 days before stimulation of the locus coeruleus. Four weeks after the stimulation, the rats were tested for acquisition of the operant task. Three control groups were used: not lesioned but stimulated, lesioned but not stimulated, and not lesioned/not stimulated. The locus coeruleus stimulation produced the same improvement of performance at the beginning of the acquisition, whether or not the dorsal noradrenergic bundle had been lesioned. However, a significant decrement of performance was observed in lesioned and stimulated rats during the last 40 min of the acquisition. In the second experiment, the locus coeruleus proper was destroyed by bilateral local injection of 6-hydroxydopamine and the locus coeruleus region was stimulated 15 days later. Three control groups were used, as in the first experiment. All the rats were tested 4 weeks later for acquisition of the operant task. The locus coeruleus lesion significantly attenuated the beneficial effect of the stimulation; however, the performance of the lesioned and stimulated rats was still significantly superior to that of the lesioned but not stimulated rats. These results suggest that the noradrenergic locus coeruleus system is involved in the long-term effect, but that the rostral projections passing through the dorsal bundle, in front of the lesion, are not critically involved in the observed effect.

Animals↗
PubMed1981

[Improvement of post-training performance 4 weeks after stimulation of the locus coeruleus in rats : absence of an effect of a lesion of the dorsal noradrenergic bundle].

The dorsal noradrenergic bundle of 25 day old rats was lesioned by means of a local injection of 6-hydroxydopamine. Eight days later each locus coeruleus was stimulated for 4 hrs. Four weeks later the animals were tested on the acquisition of food-reinforced operant task. Not lesioned but stimulated, lesioned but not stimulated and not lesioned not stimulated rats were used in controls. The locus coeruleus stimulation induced nearly the same improvement of performances whether or not the dorsal noradrenergic bundle was lesioned.

Animals↗
PubMed1981

Modulation of rat brain alpha-adrenoreceptor populations four weeks after stimulation of the nucleus locus coeruleus.

We previously showed that electrical stimulation of the nucleus locus coeruleus was followed 4 weeks later by a greatly improved performance in the acquisition of a food-reinforced operant task. To ascertain whether adrenergic receptors were involved in this long-term behavioral modification, we studied the characteristics of the alpha 1, alpha 2, and beta-adrenoreceptors of the cerebral cortex 4 weeks after stimulation of the locus coeruleus. This stimulation induced a slight (14%) but significant increase in the number of alpha 1-receptor [(3H) WB 4101 binding sites] as well a rise in the number of alpha 2-receptor [(3H) clonidine binding sites]. The latter rise mainly affected high-affinity alpha 2-receptor sites (36%) and the number of low-affinity sites remained unchanged. No significant alteration in the number of beta-receptors [(3H)-dihydroalprenolol binding sites] was observed. To confirm this biochemical result, the effect of very small doses of clonidine (1, 2.5, 5 and 10 micrograms/kg) was tested on locomotor activity in the open-field. In rats stimulated 4 weeks before injection, clonidine induced a biphasic effect, comprising firstly sedation which occurred 30 min after injection, and secondly, long-term hyperactivity which began 24 h injection. For the 5 micrograms/kg dose, this rebound of activity was detectable 8 days after injection. In implanted, control rats, only the sedative effect was observed. These findings are interpreted in relation to the current theories about alpha-adrenoreceptors.

Animals↗
PubMed1981

Learning improvement of appetitively or aversively reinforced light-dark discrimination and reversal four weeks after electrical stimulation of the lateral hypothalamus of the rat.

The experiments reported here point out the effect of electrical stimulation of the lateral hypothalamus on the acquisition and reversal of a simultaneous light-dark discrimination performed 4 weeks later. The stimulation was applied on 15-day-old rats. There were two control groups, implanted but not stimulated and non-implanted rats. In the first experiment, the light-dark discrimination task was food-reinforced. As already reported in the case of an appetitively reinforced operant task, stimulation of the lateral hypothalamus induced an important improvement of performance in discrimination and reversal. This improvement was already apparent at the beginning of acquisition. In the reversal task the mean response latency of stimulated rats was greater than tht of control animals. In the second experiment with naive rats we used the same discrimination but the task was aversively reinforced by an electric foot-shock. In spite of the different type of reinforcement used, the stimulated rats performed better than the control rats in the three behavioral situations studied: avoidance, discrimination and reversal. As in the first experiment the improvement appeared at the onset of acquisition in the three situations. Thus the long-term effect of lateral hypothalamic stimulation does not depend on the type of reinforcement, nor the behavioral task. These results are briefly discussed.

Animals↗
PubMed1977

Effects of hippocampal electrical stimulation on longterm memory and on cholinergic mechanisms in three inbred strains of mice.

Two sets of experiments have been carried out in an attempt to determine the role of hippocampal cholinergic mechanisms in a long-term memory storage. Three inbred strains of mice were presented with two different learning tasks in order to estimate their long-term retention abilities as well as changes in this ability after a post-trial hippocampal stimulation. In parallel experiments the enzymes involved in acetylcholine metabolism were studied under different experimental conditions. Our results indicate: (a) The capacity for long-term memory of the BALB/c line is much greater than that of either the C57BL/6 or C57BR strain. (b) Hippocampal post-trial electrical stimulation leads to an improvement of this capacity in the BALB/c strain. This phenomenon is less pronounced in C57BL/6 and non-existent in C57BR mice. (c) Choline acetyltransferase activity in the hippocampus is significantly higher in BALB/c than in the other two strains. In BALB/c this enzyme activity is greatly changed by the post-trial stimulation whereas in the C57BL/L strain only a slight variation of enzyme activity is observed. No modification occurs in C57BR. The results suggest that the more active acetylcholine synthesizing enzyme in the hippocampus of BALB/c may be related to a greater acetylcholine availability, thus favoring the establishment of a long-term memory, perhaps by releasing greater amounts of acetylcholine in the hippocampus immmediately after the learning session. The electrical stimulation of the hippocampus acts to magnify or accelerate this phenomenon. It is suggested that the efficiency of the stimulation would be related to the genetically determined higher cholinergic activity of the hippocampus.

Acetylcholine↗