Effets motivationnels des agonistes dopaminergiques dans un modèle de rat ayant une lésion bilatérale de l'aire tegmentale ventrale.

Le traitement médicamenteux de la maladie de Parkinson idiopathique (MPI) repose essentiellement,t sur la restauration de la transmission dopaminergique par la L-Dopa et par les agonistes dopaminergiques (DARAs) agissant sur les récepteurs dopaminergiques de la classe D2R et D3R. Cependant au cours du traitement apparaissent des comportements addictifs (addiction aux médicaments dopaminergiques, hyper-sexualité, addiction aux jeux, addiction aux achats impulsifs...). Ces troubles du comportement impulsifs (TCI) observés chez les patients parkinsoniens traités aux agonistes dopaminergiques ressemblent bien à ceux observés chez les utilisateurs chroniques de drogues d'abus telles que la morphine, les amphétamines ou la cocaïne. [...] Dans le but de comprendre la physiopathologie des manifestations addictives chez le patient parkinsonien, notre étude s'est proposée d'étudier les effets renforçateurs ou motivationnels des agonistes dopaminergiques chez l'animal dont l'ATV postérieur ou antérieure ont été bilatéralement lésés. Les manifestations addictives seront investies en utilisant le test de préférence de place conditionnée (PPC), un paradigme qui étudie l'effet motivationnel / renforçateur des agonistes utilisés. Une particularité de notre étude est qu'elle a été réalisée chez l'animal naïf sans être au préalable sensibilisé à une drogue d'abus. Son intérêt est de montrer l'effet direct des agonistes dopaminergiques sur le comportement recherché.Néan

Electrical Synapses are Involved in Orofacial Neuropathic Pain

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Acute Tramadol Administration Induces the Expression of pERK1/2 in Different Limbic and Pain Processing Structures

International audienceTramadol is a painkiller with some abuse potentials. The current study aimed to investigate rat cerebral structures that were activated by acute intraperitoneal administration of tramadol (10 mg/kg). The expression of pERK1/2 was used as a molecular tool for tramadol-induced

mGlu5 receptor antagonist blocks bromocriptine-induced conditioned place preference in bilateral mesolimbic-lesioned rat

International audienceDopamine dysregulation syndrome (DDS) has been attributed to both dopamine replacement therapies (DRT) and the mesencephalic dopaminergic lesion. The DRT reinforcement effect is due to its action on the reward system, particularly on the nucleus accumbens (NAc). This nucleus receives two major projections, a glutamatergic from the prefrontal cortex and a dopaminergic from the posterior ventral tegmental area (pVTA). The latter modulate the former within the NAc. pVTA has been demonstrated to be implicated in the motivational effect of bromocriptine (dopamine 2 receptor (D2R) agonist) in bilat- eral pVTA-lesioned animals. Therefore the potential implication of the metabotropic glutamate receptor 5 (mGluR5) antagonist (MTEP: 3-((2-Methyl-1,3-thiazol-4-yl)ethynyl)pyridine) on bromocriptine-induced conditioned place preference (CPP) was explored. Results showed that the administration of the MTEP blocked completely the bromocriptine-induced CPP in bilateral pVTA-lesioned rats. Both the CPP acqui- sition and expression were abolished. These effects are due, at least to an increase of the glutamate concentration and that of mGlu5 receptor expression in the NAc shell of the pVTA-lesioned animals. Altogether these data demonstrated the importance of the mGlu5 receptor in the bromocriptine induced- reinforcement and that DDS is probably due to DRT effect on this glutamate receptor

Reinforcing effect of tramadol in the rat

International audienceTramadol is one of the most commonly prescribed analgesic opioids in various pharmacopeias. Tramadol has been linked to abuse in recent clinical investigations. However, the behavioral effects and neural substrates of the drug have not been well characterized in preclinical studies. As a result, the present study investigated the effects of tramadol on behavioral sensitizations in rats. Its impacts on cellular and molecular alterations in the brain were also investigated. In conditioned place preference (CPP) paradigm, tramadol induced behavioral as well as motor sensitizations. These effects were dramatically reduced by intraperitoneal administration of naltrexone, an opioid receptor antagonist. Tramadol caused changes in several molecular markers (pERK1/2, Δ-FosB, PKCγ, PKMζ GAD67) in the anterior cingulate cortex, which could indicate an increase in excitation within this structure. Tramadol is demonstrated in the present study to be a reinforcing drug in rats, as it increased both behavioral and motor sensitizations. Tramadol’s effects are most likely due to the high levels of excitation it causes in the brain, which is mostly caused by the activation of opioid receptors

The Neuroprotective Effect of Clove Essential Oil Against 6-Ohda-Induced Cell Death in Sh-Sy5y and A Rat Model of Parkinson's Disease

International audienceParkinson's Disease (PD) is the second most prevalent neurological disorder. Natural therapies are becoming more popular for preventing disease onset. Clove Essential Oil (CEO), a potent antioxidant derived from Syzygium aromaticum buds, was tested in vitro (SH-SY5Y) and in vivo (PD rat model) for its ability to protect against 6-OHDA-induced cell death. Twenty-four hours of SH-SY5Y cells' exposure to 6-OHDA (100µM) drastically decreased cell viability. At doses lesser than 20µg/ml, CEO and its main component Eugenol (EG) had no cytotoxic effect on SH-SY5Y. CEO and EG at doses of 2.5-20µg/ml provided significant neuroprotection against 6-OH-DA-induced cell death. A PD rat model was generated by injecting 6-OHDA (21µg/animal) unilaterally into the striatum. An assessment of motor performance can predict neuronal cell loss in the Substancia Nigra Compacta (SNc). Compared to 6-OHDA-lesioned, CEO-treated (10mg/Kg) rats' locomotor performance (actimetry and cylinder tests) improved significantly one and two weeks after 6-OHDA-lesion. Tyrosine Hydroxylase (TH) cell count showed a significant decrease in cell death in ipsilateral SNc in both CEOtreated and 6-OHDA-lesioned rats when compared to contralateral. In contrast to the 6-OHDA-lesioned group, the ipsilateral SNc of the CEO-treated group showed a significant high TH cell number. In the present study, the neuroprotective effect of CEO was demonstrated both in vitro and in vivo against 6-OHDA cytotoxicity. Therefore, CEO could be used as a food supplement for PD prevention

Nigrostriatal dopamine depletion promoted an increase in inhibitory markers (parvalbumin, GAD67, VGAT) and cold allodynia

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Nigrostriatal dopaminergic depletion increases static orofacial allodynia

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Behavioral, Cellular and Molecular Responses to Cold and Mechanical Stimuli in Rats with Bilateral Dopamine Depletion in the Mesencephalic Dopaminergic Neurons

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