Publications du Neurocentre Magendie

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IF du Neurocentre

697 publications

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Les IF indiqués ont été collectés par le Web of Sciences en Juin 2018

31/10/1992 | Behav Brain Res   IF 3.2
Unilateral dopamine lesions in neonatal, weanling and adult rats: comparison of rotation and reaching deficits.
Abrous DN, Wareham AT, Torres EM, Dunnett SB

The aim of this study was to compare the functional effects of neonatal, weanling and adult lesions of the dopaminergic (DA) mesencephalic neurones on paw-reaching behaviour. The mesotelencephalic DA pathway was destroyed unilaterally in neonatal (3 and 7 day), weanling (21 day) and adult (2 months) rats by local injection of 6-hydroxydopamine into the medial forebrain bundle at the level of the lateral hypothalamus, followed by behavioural studies conducted 2 months later. Amphetamine and apomorphine induced similar rates of rotation irrespective of the age of the lesion. By contrast skilled reaching with the contralateral paw was profoundly disrupted by lesions made in adult or weanling rats, but a much reduced deficit was observed in neonatally lesioned rats. Tyrosine hydroxylase immunohistochemistry indicated a similar degree of dopamine cell loss from the substantia nigra in all groups. These observations suggest that the host brain undergoes developmental changes 1-3 weeks postnatally that influence the long-term effects of lesions in the nigrostriatal dopamine system.

1. Magnocellular neurosecretory cells (MNCs) were isolated from the supraoptic nucleus of adult Long-Evans rats using an enzymatic procedure. Immunocytochemical staining with antibodies against vasopressin and oxytocin revealed that MNCs can be identified by size. The membrane properties of these cells were examined at 32-34 degrees C using intracellular recording methods. 2. Isolated MNCs displayed a mean (+/- S.E.M.; n = 109) resting membrane potential of -64.1 +/- 1.0 mV, an input resistance of 571 +/- 34 M omega, and a time constant of 8.7 +/- 0.4 ms. Measurements of specific resistivity and input capacitance revealed that the soma of these cells accounts for a mere 20% of their total somato-dendritic membrane in situ. 3. Voltage-current relations measured near -60 mV were linear negative to spike threshold. From more hyperpolarized membrane potentials, voltage responses to depolarizing current steps displayed transient outward rectification and delayed impulse discharge. 4. Action potentials (76.6 +/- 0.9 mV) triggered from an apparent threshold of -59.3 +/- 0.1 mV broadened progressively at the onset of spontaneous or current-evoked spike trains. Steady-state spike duration increased as a logarithmic function of firing frequency with a maximum near 25 Hz. These effects were abolished in Ca(2+)-free solutions. 5. In all cells, evoked spike trains were followed by a prolonged Ca(2+)-sensitive after-hyperpolarization. In contrast, only a small proportion (16%) of MNCs displayed spontaneous bursting activity or depolarizing after-potentials following brief current-evoked bursts. 6. Isolated MNCs responded to amino acids (glutamate and GABA) and to the neuropeptide cholecystokinin, indicating that receptors for these neurotransmitters are expressed postsynaptically by MNCs and are retained following dissociation. 7. Increasing the osmolality of the superfusing solution by 5-30 mosmol kg-1 caused a membrane depolarization associated with a decrease of input resistance and accelerated spontaneous spike discharge in each of thirty-six MNCs tested. Current-clamp analysis suggested that these responses resulted from the activation of a cationic conductance. Excitatory effects of hyperosmolality were not observed in non-magnocellular neurones (n = 6).

17/07/1992 | Brain Res   IF 3.1
Increased locomotor response to novelty and propensity to intravenous amphetamine self-administration in adult offspring of stressed mothers.
Deminiere JM, Piazza PV, Guegan G, Abrous N, Maccari S, Le Moal M, Simon H

It is suggested that drug addiction is more likely to develop in individuals who are particularly sensitive to the reinforcing effects of drugs. Animal studies of intravenous drug self-administration (SA) have shown that rats display a large range of individual differences in the propensity to develop drug-seeking. Predisposed animals are characterized by a higher locomotor reactivity to both novelty and psychostimulants. In this report, we show that prenatal stress (restraint of the mother during the last week of pregnancy) may contribute to an individual's vulnerability to develop amphetamine self-administration. The adult offspring of stressed mothers exhibited: (i) a higher locomotor response to novelty and to an injection of amphetamine (0.3 mg/kg, i.v.); (ii) a higher level of amphetamine self-administration. The data indicate that individual predisposition to drug-seeking in the adult may be induced by prenatal events.

03/07/1992 | Brain Res   IF 3.1
Repeated corticosterone administration sensitizes the locomotor response to amphetamine.
Deroche V, Piazza PV, Maccari S, Le Moal M, Simon H

Repeated exposures to stressful situations has been shown to increase individual reactivity to psychostimulants, although the biological factors involved in such stress-induced changes are still poorly understood. In this study, we investigated the role of corticosterone in the effects of stress on the response to psychostimulants. We found that repeated corticosterone administration (both 1.5 mg/kg, intraperitoneally and 50 micrograms/ml in drinking water, once per day for 15 days) increased the locomotor response to amphetamine (1.15 mg/kg, i.p.). At the doses used in these experiments, corticosterone administration induced similar increases in plasma levels of the hormone to those induced by stress. These results suggest that corticosterone secretion may be one of the mechanisms by which repeated stress increases the behavioral responses to amphetamine. Since an enhanced reactivity to psychostimulants has been found to be an index of a propensity for drug self-administration and a model of certain psychopathological conditions, these findings point to a role for glucocorticoids in such abnormal states.

Changes in striatal dopamine D2 receptor mRNA levels provoked by unilateral 6-hydroxydopamine-induced lesion of the nigrostriatal dopamine pathway were studied by in situ hybridization. The influence of embryonic dopaminergic neurons implanted into the dopamine-depleted striatum on the lesion-induced changes was also examined. Changes in D2 mRNA levels were compared with changes in D2 receptor densities measured in the same animals by receptor autoradiography using [3H]spiperone or [3H]SDZ 205-501 as ligands. The distribution of D2 mRNA in the striatum of control animals closely paralleled that of the D2 receptor itself, as assessed by autoradiography, and the highest density of D2 mRNA occurred in the lateral part of the striatum. One month after lesion, levels of D2 mRNA were 34% higher in the dorsolateral part of the dopamine-depleted striatum than in the corresponding region of the contralateral control striatum. D2 receptor density in this region was increased by 40% relative to the control level. No significant increases could be measured in the medial part of the striatum. The increases in the lateral part were similar at 7 months post-lesion; however, at this time the increase in both D2 mRNA and receptor levels had spread to the medial part of the striatum as well. In the graft-bearing striatum levels of both D2 mRNA and D2 receptors reverted to control levels. This study shows that the post-lesion increase in striatal dopamine receptor and mRNA level is a biphasic phenomenon with a late-occurring component in the medial striatum. It also shows that once the increase in striatal D2 receptor gene expression is accomplished, it is maintained unchanged for long periods, similar to that of D2 receptor levels themselves. Moreover, grafts of embryonic dopaminergic neurons are able to modulate the expression of the dopamine D2 receptor gene.

The aim of the present study was to test whether intrastriatal implants of embryonic dopaminergic neurons are able to normalize the lesion-induced hypersensitivity of striatal dopaminergic receptors. The ascending dopaminergic pathway of adult rats was unilaterally lesioned using 6-hydroxydopamine. Three weeks later a cell suspension obtained from the mesencephali of ED 14 rat embryos was implanted into the denervated striatum. Rotational responses to dopaminergic agonists were tested five months after implantation. One month later animals were killed and striatal dopaminergic receptor densities were quantified using autoradiography, the dopaminergic reinnervation of the host striatum being visualized with [3H]GBR 12935, a ligand labelling dopamine uptake sites. The lesion induced a behavioural hypersensitivity to dopaminergic agonists and lesioned animals displayed a strong rotation contralateral to the lesion in response to a test dose of the D1 agonist compound SKF 38393 (2.5 mg/kg) or of the D2 agonist LY 171555 (0.15 mg/kg). These responses were completely abolished by the graft. The normal distribution of D1 and D2 dopaminergic receptors in the rat striatum was similar to that described previously. Seven months after the lesion of the nigrostriatal dopaminergic pathway, the density of D1 receptors was not significantly affected while the density of D2 receptors was increased by about 25-50%. The implantation of embryonic dopaminergic neurons into the denervated striatum led to a slight decrease of D1 receptor densities and to a reversal of the lesion-induced increase of striatal dopaminergic D2 receptors six months later. Moreover, this reversal concerned not only the reinnervated striatal region but also extended into non-reinnervated areas of the striatum. It is concluded that grafts of embryonic dopaminergic neurons can normalize the density of dopaminergic D2 receptors.

1992 | Exp Brain Res   IF 1.8
Intrastriatal dopamine-rich grafts induce a hyperexpression of Fos protein when challenged with amphetamine.
Abrous DN, Torres EM, Annett LE, Reading PJ, Dunnett SB

The aim of the present experiment was to characterize the effect of intrastriatal grafts of embryonic dopaminergic neurones on the expression of Fos protein in the striatum when challenged with amphetamine. Unilateral 6-hydroxydopamine lesions of the nigrostriatal pathway were made in adult rats and grafting was performed 3 weeks later. The numbers of Fos-positive nuclei in the ipsi- and contralateral striata were counted on coronal sections following immunohistochemical staining 5 months after grafting. Administration of d-amphetamine induced an increase in the density of Fos-positive nuclei in the intact striatum. This stimulatory effect of amphetamine on c-fos expression was blocked by 6-hydroxydopamine hydrobromide lesions and was restored in the striata bearing transplants. However, an overshoot was observed as the density of Fos-positive cells within the grafted striatum was larger than that observed within the intact striatum. This hyperexpression of Fos-positive nuclei was correlated with the exaggerated compensation of amphetamine-induced rotation in the same animals.

1. The sensitivity of cromakalim-activated current (Icrom) to manipulations of extracellular cationic composition was examined in whole-cell voltage clamp recordings from freshly-dispersed, adult guinea-pig ventricular myocytes. In bathing media with different concentrations of K+ (1, 2.5, 5.4 and 12 mM) the Icrom reversal potential (Erev) varied in strict correspondance with the K+ equilibrium potential and inward Icrom amplitude was proportional to the external K+ concentration. 2. Replacement of 12mM K+ with 12mM Rb+ induced a slight positive shift of Erev indicating that PRb+/PK+ = 1.06. K+ replacement with 12mM Cs+ reduced or abolished inward Icrom and produced a negative shift of Erev by at least 50 mV; an upper limit of PCs+/PK+ was fixed at 0.18. 3. Addition of Rb+ (1-30 mM) to 2.5 mM K(+)-containing medium produced a concentration-dependent increase in inward Icrom and positive shift of Erev suggesting that K+ and Rb+ have similar permeabilities and conductivities and do not interfere with each other in the channel. 4. CS+ (0.01-30 mM), added to medium containing 12 mM Rb+, induced a potent, voltage-dependent inhibition of inwardly rectifying current (IK1; IC50 = 0.2-3 mM). Voltage-dependent inhibition of inward Icrom was observed only at considerably higher CS+ concentrations (IC50 = 4-30 mM). Extracellular Rb+ and CS+ did not substantially alter the amplitude of outward Icrom. 5. The results support the contention that the ATP-sensitive K+ channel is the primary target of cromakalim action in ventricular myocytes.

02/1991 | Behav Pharmacol   IF 1.9
Effects of tianeptine on spontaneous alternation, simple and concurrent spatial
Jaffard R, Mocaer E, Poignant JC, Micheau J, Marighetto A, Meunier M, Beracochea D

The effects of systemic administration of tianeptine, a new psychotropic agent

The aim of the present study was to test whether intrastriatal implants of embryonic dopaminergic neurons are able to normalize the lesion-induced dysfunction of striatal enkephalinergic neurons, one of the major output systems of the striatum. The ascending dopaminergic pathway of adult rats was unilaterally lesioned. Three weeks later a cell suspension obtained from the mesencephali of ED14 rat embryos was implanted into the denervated striatum and striatal methionin enkephalin immunostaining was quantified six months later by the use of an image analyser. Methionin enkephalin immunostaining was unevenly distributed in the striatum of control animals. Besides the classical patch/matrix pattern, a mediolateral gradient was also present and, moreover, immunostaining decreased towards caudal levels. Seven months after the lesion of the nigrostriatal dopaminergic pathway, methionin enkephalin immunostaining was found to be increased in the denervated striatum by about 50%. However, relative increases were more sustained in the areas where basal methionin enkephalin immunostaining were lowest, i.e. the lateral striatum and posterior striatal areas. This resulted in an attenuation of the global gradients seen in the normal striatum. Increased immunostaining was also found in the ipsilateral globus pallidus. The implantation, into the denervated striatum, of embryonic dopaminergic neurons led to a reversal of the lesion-induced increase of striatal and pallidal methionin enkephalin immunostaining six months later. Moreover, this reversal resulted in an overshoot, as the level of immunostaining in the graft-bearing striatum was found to be lower than the levels found in the normal striatum. It is concluded that grafts of embryonic dopaminergic neurons can normalize the function of one of the major output systems of the striatum and, through it, influence more distant targets of this structure. This suggests a physiological basis for the behavioral effects observed previously with such grafts.