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1.
Neuropeptides ; 58: 83-92, 2016 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-26764217

RESUMEN

The neuropeptide galanin is widely distributed in the central and peripheral nervous systems and part of a bigger family of bioactive peptides. Galanin exerts its biological activity through three G-protein coupled receptor subtypes, GAL1-3R. Throughout the last 20years, data has accumulated that galanin can have a neuroprotective effect presumably mediated through the activation of GAL1R and GAL2R. In order to test the pharmaceutical potential of galanin receptor subtype selective ligands to inhibit excitotoxic cell death, the GAL1R selective ligand M617 and the GAL2R selective ligand M1145 were compared to the novel GAL1/2R ligand M1154, in their ability to reduce the excitotoxic effects of intracerebroventricular injected kainate acid in rats. The peptide ligands were evaluated in vitro for their binding preference in a competitive (125)I-galanin receptor subtype binding assay, and G-protein signaling was evaluated using both classical signaling and a label-free real-time technique. Even though there was no significant difference in the time course or severity of the kainic acid induced epileptic behavior in vivo, administration of either M617 or M1154 before kainic acid administration significantly attenuated the neuronal cell death in the hippocampus. Our results indicate the potential therapeutic value of agonists selective for GAL1R in the prevention of neuronal cell death.


Asunto(s)
Bradiquinina/análogos & derivados , Galanina/análogos & derivados , Hipocampo/patología , Neuronas/metabolismo , Neuronas/patología , Fragmentos de Péptidos/farmacología , Receptor de Galanina Tipo 1/metabolismo , Receptor de Galanina Tipo 2/metabolismo , Animales , Bradiquinina/farmacología , Muerte Celular/efectos de los fármacos , Línea Celular Tumoral , AMP Cíclico/metabolismo , Galanina/farmacología , Hipocampo/efectos de los fármacos , Humanos , Ácido Kaínico/toxicidad , Ligandos , Masculino , Neuronas/efectos de los fármacos , Unión Proteica , Ratas , Ratas Sprague-Dawley , Receptor de Galanina Tipo 1/agonistas , Receptor de Galanina Tipo 2/agonistas
2.
Addict Biol ; 20(4): 701-13, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25053279

RESUMEN

Relapse represents one of the most significant problems in the long-term treatment of drug addiction. Cocaine blocks plasma membrane monoamine transporters and increases dopamine (DA) overflow in the brain, and DA is critical for the motivational and primary reinforcing effects of the drug as well as cocaine-primed reinstatement of cocaine seeking in rats, a model of relapse. Thus, modulators of the DA system may be effective for the treatment of cocaine dependence. The endogenous neuropeptide galanin inhibits DA transmission, and both galanin and the synthetic galanin receptor agonist, galnon, interfere with some rewarding properties of cocaine. The purpose of this study was to further assess the effects of galnon on cocaine-induced behaviors and neurochemistry in rats. We found that galnon attenuated cocaine-induced motor activity, reinstatement and DA overflow in the frontal cortex at a dose that did not reduce baseline motor activity, stable self-administration of cocaine, baseline extracellular DA levels or cocaine-induced DA overflow in the nucleus accumbens (NAc). Similar to cocaine, galnon had no effect on stable food self-administration but reduced food-primed reinstatement. These results indicate that galnon can diminish cocaine-induced hyperactivity and relapse-like behavior, possibly in part by modulating DA transmission in the frontal cortex.


Asunto(s)
Cocaína/farmacología , Cumarinas/farmacología , Inhibidores de Captación de Dopamina/farmacología , Lóbulo Frontal/metabolismo , Animales , Trastornos Relacionados con Cocaína/fisiopatología , Trastornos Relacionados con Cocaína/prevención & control , Condicionamiento Operante , Dopamina/metabolismo , Comportamiento de Búsqueda de Drogas/efectos de los fármacos , Ingestión de Alimentos/efectos de los fármacos , Extinción Psicológica/efectos de los fármacos , Galanina/antagonistas & inhibidores , Masculino , Microdiálisis , Actividad Motora/efectos de los fármacos , Núcleo Accumbens/metabolismo , Ratas Sprague-Dawley , Recurrencia , Refuerzo en Psicología , Autoadministración
3.
Brain Res ; 1425: 90-7, 2011 Nov 24.
Artículo en Inglés | MEDLINE | ID: mdl-22024546

RESUMEN

We evaluated levels of exercise-induced brain-derived neurotrophic factor (BDNF) messenger RNA (mRNA) within the hippocampal formation in rats selectively bred for 1) high intrinsic (i.e., untrained) aerobic capacity (High Capacity Runners, HCR), 2) low intrinsic aerobic capacity (Low Capacity Runners, LCR), and 3) unselected Sprague-Dawley (SD) rats with or without free access to running wheels for 3 weeks. The specific aim of the study was to determine whether a dose-response relationship exists between cumulative running distance and levels of BDNF mRNA. No additional treatments or behavioral manipulations were used. HCR, LCR, and SD rats were grouped by strain and randomly assigned to sedentary or activity (voluntary access to activity wheel) conditions. Animals were killed after 21 days of exposure to the assigned conditions. Daily running distances (mean ± standard deviation meters/day) during week three were: HCR (4726 ± 3220), SD (2293 ± 3461), LCR (672 ± 323). Regardless of strain, levels of BDNF mRNA in CA1 were elevated in wheel runners compared to sedentary rats and this difference persisted after adjustment for age (p=0.040). BDNF mRNA was not affected by intrinsic aerobic capacity and was not related to total running distance. The results support that BDNF mRNA expression is increased by unlimited access to activity wheel running for 3 weeks but is not dependent upon accumulated running distance.


Asunto(s)
Factor Neurotrófico Derivado del Encéfalo/metabolismo , Cruzamiento , Actividad Motora/genética , Condicionamiento Físico Animal/fisiología , ARN Mensajero/metabolismo , Carrera/fisiología , Factores de Edad , Animales , Factor Neurotrófico Derivado del Encéfalo/genética , Cruzamiento/métodos , Región CA1 Hipocampal/metabolismo , Tolerancia al Ejercicio/genética , Masculino , Condicionamiento Físico Animal/métodos , ARN Mensajero/biosíntesis , Ratas , Ratas Sprague-Dawley
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