Neurocentre Magendie

Les publications

IF du Neurocentre

723 publications

* equal contribution
Les IF indiqués ont été collectés par le Web of Sciences en Juin 2016

09/1990 | Neurobiol Aging   IF 5.2
A comparison of the working memory performances of young and aged mice combined
Lebrun C, Durkin TP, Marighetto A, Jaffard R

The spatial working memory performances of young (2 months) and aged (24-26

The ascending mesotelencephalic dopaminergic systems of rat pups of 3 days of age were bilaterally lesioned using 6-hydroxydopamine injected at the level of the lateral hypothalamus. A sub-group of lesioned pups received, 5 days after the lesion, a dopamine neuron-rich cell suspension graft implanted bilaterally into the striatum and nucleus accumbens. Behavioral tests were conducted 6 months later. The lesion induced an increase in the locomotor activation induced by D-Ala2-Met5-enkephalinamide injected into the nucleus accumbens (2.5 micrograms/side) as compared to the activation observed in control animals. Locomotor activation by systemic apomorphine (0.1 mg/kg s.c.) was also increased while that induced by amphetamine (1.5 mg/kg i.p.) was abolished. The presence of DA neuron implants reversed each of these post-lesion modifications.

Individual vulnerability to drug addiction may be an important factor in the prognosis of this pathological behavior in man. However, experimental investigations have largely neglected the psychobiological substrate of predisposition to addiction. In this study, we show using a self-administration (SA) acquisition paradigm that previous repeated exposure to a stressful experience (tail-pinch) or to amphetamine, increase the locomotor response to this drug (behavioral sensitization) and enhance vulnerability to acquire amphetamine SA. These results show that vulnerability to develop amphetamine SA may be influenced by stressful experiences, and that previous contact with the drug may enhance a predisposition to amphetamine-taking behavior. As tail-pinch and amphetamine sensitization affect both the dopamine (DA) neural system and the propensity to self-administer amphetamine (behavior also modulated by DA activity), stress may influence SA via an action on the DA system.

04/1990 | Pharmacol Biochem Behav   IF 3
Chronic thioridazine treatment differently affects DA receptors in striatum and in mesolimbo-cortical systems.
Piazza PV, Calza L, Giardino L, Amato G

Chronic thioridazine administration (5 mg/kg for 22 days) caused both behavioral and dopamine (DA) receptor modifications in rats. After chronic thioridazine administration, a significant increase in both locomotion and stereotypies induced by apomorphine was observed. In particular, only sniffing increased significantly, whereas grooming behavior decreased and the number of rearings did not change. Autoradiographic data were consistent with the behavioral results. Chronic thioridazine caused an up-regulation of DA receptors both in the striatum and in the olfactory tubercle (O.T.). The striatal effect may account for the increase of stereotypies, whereas the effect in the olfactory tubercle may account for the increase in locomotion. An increase in DA receptors was also found in the medial (MCTX) and dorsal cortex (DCTX). However, a decrease in DA receptors appeared in the nucleus accumbens septi (NAS) and in the lateral cortex (LCTX). This decrease, selectively localized in the mesolimbic DA system, may represent the neurobiological substrate of the depolarization block observed in A10 neurons after chronic thioridazine treatment.

05/02/1990 | Neurosci Lett   IF 2.1
Thioridazine chronic administration: a behavioural and autoradiographic study.
Calza L, Giardino L, Piazza PV, Amato G

In rats the effects of chronic treatment with thioridazine (5 mg/kg orally administered for 22 days) were studied by means of behavioural supersensitivity to apomorphine and by means of dopamine (DA) receptors quantitative autoradiography. Locomotion and stereotypies induced by apomorphine increased after thioridazine chronic administration, whereas grooming behaviour decreased. Autoradiographic data showed an increase in DA receptors density both in the striatum and in the olfactory tubercle, to which the increase in stereotypies and locomotion could be respectively attributed. DA receptors increased also in the medial and dorsal frontal cortex. Moreover a decrease in DA receptors density appeared in the nucleus accumbens septi and in the lateral frontal cortex. Receptors decrease found in these regions might be associated with thioridazine-induced chronic inactivation of A10 DA neurons, to which the antipsychotic effect of the drug is attributed.

The aim of the present experiments was to test whether adrenal chromaffin cells implanted into the striatum of rats could exert a functional effect through a release of catecholamines. A cell suspension obtained from bovine adrenal medulla was implanted unilaterally into the striatum. The striatal dopaminergic input was extensively destroyed beforehand to preclude the possibility of reinnervation of the striatum by endogenous dopaminergic neurons. The functional influence of the implant was tested through the measurement of drug-induced rotation, while catecholamine release was measured subsequently in the same animals by in vivo electrochemistry. Transplant survival, as shown by the immunohistochemical analysis performed at the end of the in vivo experiments, was highly variable. Surviving chromaffin cells maintained their endocrine morphology and no reinnervation of the host striatum could be detected. Rotation of the animals evoked by apomorphine (0.1 mg/kg, sc) or amphetamine (5.0 mg/kg, ip) following the lesion was left uninfluenced following transplantation, even when a large transplant was recovered. On the other hand, nicotine (0.5 mg/kg, sc) evoked a strong contraversive rotational response in the transplant-bearing animals. This response could not be ascribed to the central effect of substances released peripherally and entering the nervous system through the blood-brain barrier opened by the implantation procedure, as it could not be found in animals bearing implants of other peripheral endocrine tissue, viz, pituitary. The effect of nicotine was not blocked by the pretreatment of the animals with either the opiate antagonist naloxone (2.5 mg/kg, 10 min) or the dopamine receptor blocker pimozide (0.5 mg/kg, 1 h), although the latter pretreatment blocked the amphetamine-evoked rotation. No spontaneous catecholamine release could be detected from the implanted chromaffin cells by in vivo electrochemistry, while treatment with amphetamine or nicotine did evoke a release. The results suggest that the functional effects of such intrastriatal grafts of chromaffin cells, reported in previous studies, cannot be explained by the secretion from the grafted cells of catecholamines into the denervated striatum. On the other hand the results obtained following the pharmacological stimulation of these cells indicate that adrenal grafts can, under suitable conditions, influence the functioning of the host nervous system.

01/1990 | J Psychopharmacol   IF 3.6
Opiate receptor modifications in the rat brain after chronic treatment with haloperidol and suipiride.
Giardino L, Calza L, Piazza PV, Zanni M, Sorbera F, Amato G

Anatomical, electrophysiological and pharmacological data support the existence of a pronounced interaction between dopamine (DA) and opioids. In particular, chronic administration of DA antagonist drugs modifies opiate peptides and opiate receptors. In this paper we focused, by means of quantitative receptor autoradiography, on the modifications induced by chronic neuroleptic treatment, in patches versus diffuse distribution, of opiate receptors in the striatum, and we also studied the different effects of haloperidol and sulpiride on striatal and cortical receptors. We found a significant decrease of the number of (3H)- naloxone binding sites in the striatal patches of treated animals but no effects in the matrix. We also observed, in haloperidol-treated animals, an increase of (3H)-naloxone binding sites in the medial cortex, and in sulpiride-treated animals an increase in the lateral and dorsal cortex. Two main observations arise from our data: (a) a differential effect is produced by neuroleptic treatment on opiate receptors in patches and in matrix; (b) an opposite influence is exerted by sulpiride and haloperidol on opiate receptors in the cortex and in striatum.

01/1990 | immunology   IF 4.1
Secretion of interleukin-6 (IL-6) by human monocytes stimulated by muramyl dipeptide and tumour necrosis factor alpha.
Sanceau J, Falcoff R, Beranger F, Carter DB, Wietzerbin J

We studied IL-6 gene expression in human monocytes stimulated by muramyl dipeptide (MDP), a synthetic immunomodulator derived from mycobacterial cell walls. In control monocytes, two IL-6 transcripts of 3.4 kb and 1.6 kb were easily detected at 2.5 hr of culture and remained stable until 18 hr. In MDP-treated monocytes, three IL-6 RNA species displayed different kinetics of accumulation: a 3.4 kb RNA whose expression already reached its maximum after 2.5 hr exposure to MDP; a 1.6 kb RNA whose expression peaked at 5 hr; and a new RNA species of 1.4 kb which was transiently induced in early time of cell stimulation. TNF-alpha co-operated with MDP to increase IL-6 gene expression and secretion of biological active protein (measured by the hybridoma plasmacytoma growth factor assay). MDP exhibits a broad spectrum of immunomodulation properties such as adjuvant activity, enhancement of macrophage cytotoxicity against tumour and induction of non-specific resistance to intracellular agents. The results reported here suggest that these properties might be linked to the stimulation by MDP of genes coding for key cytokines such as IL-6, TNF and IL-1.

1990 | Behav Pharmacol   IF 2
Individual reactivity to novelty predicts probability of amphetamine self-administration.
Piazza PV, Deminiere JM, Maccari S, Mormede P, Le Moal M, Simon H

The present study demonstrates a relationship between individual responses to environmental activation, such as novelty, and propensity to acquire amphetamine self-administration. Locomotor activity cumulated over 2 h of exposure to a circular corridor was a stable and novelty-dependent feature of behaviour in individual rats. The differences between subjects in this behaviour were maintained over two trials at 1 months intervals, but disappeared over 4 days when the animals were tested daily, i.e. when the environment was no longer novel. The subjects with the higher locomotor response to novelty (HR group) also showed a higher propensity to acquire amphetamine self-administration, while the subjects with the lower response to novelty (LR group) did not acquire self-administration over 7 days of testing. Differences in self-administration of HR animals could not be accounted for by differences in exploratory behaviour. Thus, HR animals did not show higher investigative responses in a hole exploration test. Animals with the higher locomotor response to novelty also showed a greater release of corticosterone in the same environment. Since dopaminergic (DA) neurons are activated by both amphetamine and novelty, it is possible that differences in the propensity to acquire amphetamine self-administration may be accounted for by differences in the activity of DA neurons.