ABSTRACT
Several morphological works have shown that the globus pallidus (GP) contains the highest density of 5-HT1B receptors within the telencephalon. However, the role of these receptors in the spiking of GP neurons in vivo is unknown. In the present work, we use single-unit extracellular recordings in the anesthetized rat to analyze changes in the firing rate of GP neurons evoked by local activation and blockade of 5-HT1B receptors. Intrapallidal administration of serotonin, or the serotonin uptake inhibitor fluoxetine, predominantly produced an excitatory effect in the basal firing rate of GP neurons. The 5-HT1B receptor agonist, L-694,247, caused a dose-dependent excitatory effect on most pallidal neurons tested. Blockade of 5-HT1B receptors by intrapallidal application of methiothepin predominantly caused inhibition in GP neurons firing rate. Moreover, methiothepin diminished the excitatory effect evoked by L-694,247. Furthermore, local serotonin did not evoke significant changes in the basal firing rate of GP neurons in unilateral striatal lesioned rats. Taken all together, these results suggest that serotonin 5-HT1B receptors significantly contribute to the control of spiking of the rat GP neurons, and that the 5-HT1B receptors exerting this control are most likely localized in the striato-pallidal pathway.
Subject(s)
Action Potentials/physiology , Globus Pallidus/drug effects , Globus Pallidus/physiology , Oxadiazoles/pharmacology , Receptor, Serotonin, 5-HT1B/metabolism , Serotonin 5-HT1 Receptor Antagonists , Tryptamines/pharmacology , 8-Hydroxy-2-(di-n-propylamino)tetralin/pharmacology , Action Potentials/drug effects , Anesthesia , Animals , Behavior, Animal/drug effects , Denervation , Fluoxetine/pharmacology , Globus Pallidus/cytology , Male , Methiothepin/pharmacology , Neurons/drug effects , Neurons/physiology , Piperazines/pharmacology , Pyridines/pharmacology , Quinolinic Acid , Rats , Rats, Wistar , Serotonin/pharmacology , Serotonin Antagonists/pharmacology , Serotonin Receptor Agonists/pharmacology , Selective Serotonin Reuptake Inhibitors/pharmacologyABSTRACT
Two glutamic acid analogs, (+)-(S)- and (-)-(R)-4-(2,2-diphenyl-1,3,2-oxazaborolidin-5-oxo)propionic acid ((+)-(S)- and (-)-(R)-Trujillon, respectively), were prepared. The stereospecific activity of their pharmacological properties was studied. The median convulsant dose (CD(50)) and median lethal dose (LD(50)) were analyzed in female Swiss Webster mice and their effects in vivo on unitary electrical activity in globus pallidus neurons were elucidated in male Wistar rats. Compounds were characterized by (1)H, (13)C, and (11)B nuclear magnetic resonance. The LD(50) of (+)-(S)-Trujillon was 449.08 mg/kg and it increased spontaneous motor activity, while with (-)-(R)-Trujillon there was no mortality up to 1,000 mg/kg and it decreased spontaneous motor activity. The CD(50) in experiments with (+)-(S)-Trujillon was 199.34 mg/kg. Unitary recording in globus pallidus neurons showed i.v. administration (+)-(S)-Trujillon (50 mg/kg) increased frequency 79.0 +/- 23.0% in relation to basal response. (-)-(R)-Trujillon and (+)-(S)-glutamate (50 mg/kg each) did not provoke changes in spontaneous basal firing. Local infusion of (+)-(S)-Trujillon (1 nMol) increased spontaneous firing in most neurons tested by 269.0 +/- 83.0% in relation to basal values. Intrapallidal infusion of (-)-(R)-Trujillon (1 nMol) and saline solution did not cause statistically significant changes in globus pallidus spiking. Results showed that (+)-(S)-Trujillon crosses the blood-brain barrier and has stereospecific activity.
Subject(s)
Boron Compounds/chemical synthesis , Glutamates/chemistry , Glutamic Acid/analogs & derivatives , Glutamic Acid/chemical synthesis , Animals , Boron Compounds/pharmacology , Boron Compounds/toxicity , Convulsants/chemical synthesis , Convulsants/chemistry , Convulsants/pharmacology , Diffusion , Dose-Response Relationship, Drug , Evoked Potentials/drug effects , Female , Globus Pallidus/cytology , Globus Pallidus/drug effects , Glutamates/pharmacology , Glutamates/toxicity , Glutamic Acid/pharmacology , Glutamic Acid/toxicity , Indicators and Reagents , Injections, Intravenous , Lethal Dose 50 , Mice , Neurons/drug effects , Stereoisomerism , Telencephalon/cytology , Telencephalon/drug effectsABSTRACT
Bernardino Ramazzini was a renowned physician and a prolific writer, born in Capri in 1633. He is considered the father of occupational medicine for having written the first paper on workers' diseases (De morbis artificum diatriba). His Treaty on Workers' diseases included 53 different professions, one particular and specific method of analysis, and a methodological proposal to prevent these diseases. This essay supports the approach taken by the father of occupational medicine and confirms that the principles established in his work are applicable to this day. A fair tribute is paid to the man and his writings in the third century after their publication. The English version of this paper is available at: http://www.insp.mx/salud/index.html.
Subject(s)
Occupational Diseases/history , Occupational Medicine/history , Chemical Industry/history , Education, Medical/history , History, 17th Century , History, 18th Century , History, 19th Century , History, 20th Century , Human Rights/history , Humans , Italy , Occupational Diseases/epidemiology , Occupational Diseases/prevention & control , Occupational Diseases/therapy , Occupational Medicine/trends , Social Change/history , Technology/historyABSTRACT
Bernardino Ramazzini was a renowned physician and a prolific writer, born in Capri in 1633. He is considered the father of occupational medicine for having written the first paper on workers' diseases (De morbis artificum diatriba). His Treaty on Workers' diseases included 53 different professions, one particular and specific method of analysis, and a methodological proposal to prevent these diseases. This essay supports the approach taken by the father of occupational medicine and confirms that the principles established in his work are applicable to this day. A fair tribute is paid to the man and his writings in the third century after their publication.
Subject(s)
Humans , History, 17th Century , History, 18th Century , History, 19th Century , History, 20th Century , Occupational Medicine , Occupational Diseases/history , Technology , Human Rights , Italy , Occupational Medicine , Occupational Diseases/epidemiology , Occupational Diseases/prevention & control , Occupational Diseases/therapy , Education, Medical/history , Chemical Industry/history , Social Change/historyABSTRACT
El óxido nítrico es sintetizado a partir de L-arginina, reacción catalizada por la enzima óxido nítrico sintasa, esta molécula de vida efímera participa en varios procesos como: regulación de presión arterial, citotoxicidad y comunicación celular. Un gran número de sus acciones son inhibidas por azul de metileno, inhibidor de la guanilato ciclasa. Moléculas análogas a la L-arginina con grupo guanidino libre, pueden funcionar como aportadores de óxidos de nitrógeno y tener acciones semejantes al óxido nítrico. En este trabajo se reporta el efecto hipotensor y toxicidad aguda de oxoborolidinona de L-arginina comparativamente con L-arginina, nitrito y nitrato, y su modulación con azul de metileno. La dosis letal media, en rata Wistar, para oxoborolidinona fue 169.0 ñ 5 mg kg-1 vía intraperitoneal y la dosis hipotensora media 10 hmoles kg-1 vía femoral; ambos parámetros fueron desplazados claramente a la derecha por el pretratamiento con azul de metileno, juzgado por las dosis letal y dosis efectiva medias, la oxoborolidinona tuvo un efecto más potente que la L-arginina y nitrato pero semejante a nitrito. En todos los casos, excepto para nitrato, los efectos fueron modulados por azul de metileno, lo que sugiere que los efectos estudiados son mediados vía óxidos de nitrógeno.
