Activation of a hypothalamus-habenula circuit by mechanical stimulation inhibits cocaine addiction-like behaviors

BACKGROUND: Mechanoreceptor activation modulates GABA neuron firing and dopamine (DA) release in the mesolimbic DA system, an area implicated in reward and substance abuse. The lateral habenula (LHb), the lateral hypothalamus (LH), and the mesolimbic DA system are not only reciprocally connected, but also involved in drug reward. We explored the effects of mechanical stimulation (MS) on cocaine addiction-like behaviors and the role of the LH-LHb circuit in the MS effects. MS was performed over ulnar nerve and the effects were evaluated by using drug seeking behaviors, optogenetics, chemogenetics, electrophysiology and immunohistochemistry. RESULTS: Mechanical stimulation attenuated locomotor activity in a nerve-dependent manner and 50-kHz ultrasonic vocalizations (USVs) and DA release in nucleus accumbens (NAc) following cocaine injection. The MS effects were ablated by electrolytic lesion or optogenetic inhibition of LHb. Optogenetic activation of LHb suppressed cocaine-enhanced 50 kHz USVs and locomotion. MS reversed cocaine suppression of neuronal activity of LHb. MS also inhibited cocaine-primed reinstatement of drug-seeking behavior, which was blocked by chemogenetic inhibition of an LH-LHb circuit. CONCLUSION: These findings suggest that peripheral mechanical stimulation activates LH-LHb pathways to attenuate cocaine-induced psychomotor responses and seeking behaviors.

Effect of repeated oral therapeutic doses of methylphenidate on food intake and growth rate in rats

Central nervous system stimulants are known to produce anorexia. Previous data suggest that methylphenidate can have variable effects on caloric intake and growth rate. A dose-response study was performed to monitor caloric intake, liquid intake and growth rate in rats following repeated administration of human oral therapeutic doses 2 mg/kg/day, 5mg/kg/day and 8mg/kg/day of methylphenidate. We found that food intake and water intake, increased in all weeks and at all doses used in the study. Growth rate increased more at higher dose [8mg/kg/day] and at low dose [2mg/kg/day] of methylphenidate in 1st and 2nd week whereas more decreased by the above doses in 3rd week, suggesting that food stimulation leads to initial increase in growth rate but long term administration of methylphenidate attenuate growth rate that is not due to modulation of appetite but may be due to anxiety and increased activity produce by stimulants. A possible role of DA, 5HT receptors in modulation of appetite and anxiety is discussed

Pharmaceutical and clinical evaluation of intravenous admixture of dobutamine and dopamine used in treatment hypotension in neonatal intensive care units

The aim of this study was to evaluate compatibility and stability of the maximum concentration used for binary admixture containing dobutamine and dopamine in 5% glucose. The maximum concentration of each drug was 5.76 mg/ml of dobutamine and 2.88 mg/ml of dopamine in 50 ml of 5% glucose. The physical compatibility of binary admixtures was assessed using visual inspection and pH determination immediately after preparation [at 0 time] and after 24 hrs. The chemical stability was assessed using high performance thin layer chromatoghraphy [HPTLC]. The method is based on HPTLC separation of the two drugs followed by densitometric measurements of their spots at 254 nm using Camag TLC Scanner 3. The mobile phase comprised ethyl acetate: n-propanol: water: glecial acetic acid [60:24:9:3, v/v/v/v]. The results revealed that no precipitation, gas evaluation, color change, pH change or chemical incompatibility were observed over the entire time of mixing of two drugs in 5% glucose solution

Núcleo accumbens y el sistema motivacional a cargo del apego / Nucleus accumbens and the motivational system of attachment

The concept of attachment involves the pursuit of proximity of both a figure linked, as a partner. For that to happen there must be a motivational system for innate social interaction in all mammals including humans. This motivational system has its seat on the dopaminergic mesocorticolimbic pathway, known as the reward pathway and is where the Nucleus Accumbens plays a key role. This pathway would be selected and highly conserved by evolution as a mechanism for perpetuating genetics. There is a great influence of prosocial neuropeptides Oxitocin (OT) and Vasopressin (ADH) in this way. These are released into socio-sexual experiences, which can be demonstrated in the paradigms of adult-adult attachment (pair bonding) and mother and child attachment. The path of motivation cast into critical periods of development, leaving it vulnerable to what happens in the environment and its damage or disease, henee, would leave traces more or less stable throughout the Ufe eyele of the individual. This could be a initial factor to psychopathology from "attachment disorder" to "addiction" to drugs. The motivation could also be useful as a endophenotype.

El concepto de apego implica la búsqueda de proximidad tanto de una figura vincular, como de un compañero (partner). Para que ocurra debe existir un sistema motivacional por la interacción social innato en todos los mamíferos incluyendo al humano. Este sistema motivacional tiene su asiento neurobiológico en la vía dopaminérgica mesocorticolímbica, denominada de la recompensa y es donde el Núcleo Accumbens juega un rol clave. Esta vía estaría seleccionada y altamente conservada por la evolución como mecanismo para la perpetuación genética. Existe una gran influencia de los neuropéptidos prosociales Oxitocina (OT) y Vasopresina (ADH) en esta vía. Estos se liberan en experiencias socio-sexuales, hecho que se puede demostrar en los paradigmas de apego adulto- adulto (pair bonding) y apego materno-infantil. La vía de la motivación se moldea en períodos críticos del desarrollo, dejándolo vulnerable a lo que suceda en el ambiente y su daño o enfermedad, por lo tanto, dejaría huellas más o menos estables a lo largo del ciclo vital del individuo. Esto podría ser un factor inicial de psicopatología desde trastornos del vínculo hasta la adicción a drogas de abuso. La motivación también podría ser útil como un endofenotipo.

Effect of Itopride Hydrochloride on the Ileal and Colonic Motility in Guinea Pig In Vitro

PURPOSE: Itopride hydrochloride (itopride) inhibits acetylcholinesterase (AChE) and antagonizes dopamine D(2) receptor, and has been used as a gastroprokinetic agent. However, its prokinetic effect on the small bowel or colon has not yet been thoroughly investigated. The aim of this study was to investigate the effects of itopride on motor functions of the ileum and colon in guinea pigs. MATERIALS AND METHODS: The distal ileum was excised and the activity of peristaltic contraction was determined by measuring the amplitude and propagation velocity of peristaltic contraction. The distal colon was removed and connected to the chamber containing Krebs-Henseleit solution (K-H solution). Artificial fecal matter was inserted into the oral side of the lumen, and moved toward the anal side by intraluminal perfusion via peristaltic pump. Colonic transit times were measured by the time required for the artificial feces to move a total length of 10cm with 2-cm intervals. RESULTS: In the ileum, itopride accelerated peristaltic velocity at higher dosage (10(-10)-10(-6)M) whereas neostigmine accelerated it only with a lower dosage (10(-10)-10(-9)M). Dopamine (10(-8)M) decelerated the velocity that was recovered by itopride infusion. Itopride and neostigmine significantly shortened colonic transit at a higher dosage (10(-10)-10(-6)M). Dopamine (10(-8)M) delayed colonic transit time that was also recovered after infusion of itopride. CONCLUSION: Itopride has prokinetic effects on both the ileum and colon, which are regulated through inhibitory effects on AChE and antagonistic effects on dopamine D(2) receptor.

Vias dopaminérgicas e somatostatinérgicas diminuem o TSH sérico em ratos portadores de carcinoma mamário walker-256 / Dopaminergic and somatostatinergic pathways decrease serum thyrotropin in rats bearing the 256-walker mammary carcinoma

A funcão do eixo hipotálamo-hipófise-tireóide em animais portadores da "síndrome do T3 baixo", foi estudada em ratos implantados com o tumor de Walker-256. Ratos machos adultos foram injetados com 1 x 106 células tumorais viáveis, por via SC, e sacrificados após 10 dias. A intensidade da síndrome guardou relacão positiva com o tamanho do tumor desenvolvido. Houve diminuicão da atividade tireoideana documentada pela diminuicão da área nuclear das células foliculares, das concentracões plasmáticas do T4, da rTg e da captacão do 131I. Mesmo o implante SC de um pellet de TSH de liberacão lenta causou menor estimulacão tireoideana, avaliada após 2 e 24h nos ratos com tumor. A secrecão do rTSH avaliada através da administracão IV de TRH mostrou-se significativamente diminuída nestas condicões, indicando aumento do tônus inibidor hipotalâmico sobre a secrecão deste hormônio. A participacão de outros neuro-mediadores hipotalâmicos foi verificada através da administracão prévia de metoclopramida e/ou fisostigmina, com ou sem estímulo subseqüente pelo TRH. Nos animais tratados com metoclopramida, os valores do rTSH aumentaram significativamente, assim como a resposta ao estímulo de secrecão pelo TRH. A fisostigmina mostrou-se mais eficiente na mediacão da resposta de secrecão do rTSH, bem como na resposta ao estímulo de secrecão pelo TRH. A administracão concomitante dos dois fármacos, seguida do estímulo pelo TRH, normalizou a secrecão do rTSH. Conclui-se que, além das alteracões conhecidas do metabolismo das iodotironinas, a secrecão de TSH encontra-se diminuída nos animais portadores de tumor de Walker-256, sugerindo diminuicão global do tônus tireoideano.

Neurochemical estimations of some new quaternary phenacyl- bromopiperidinium compounds

Considering the fact that N-alkyl substituted quaternary ammonium salts of piperidinium bromide induce brain catecholamine and indoleamine metabolism, we thought it may he valuable to investigate the effects of three selected phenacyl derivatives [I, V and VIII] of piperidine on brain monoamines metabolism in mice [100mg/kg body weight] assuming that these derivatives might alter the brain indoleamine and catecholamine levels differently. Studies are carried out by using HPLC technique. It was found that compound VIII possessed greater neuroleptic activity as compared to compounds I and V

Efeitos renais e cardiovasculares da infusão de dopamina e da solução de cloreto de sódio a 7, 5 por cento: estudo experimental em cães com restrição hídrica / Renal and cardiovascular effects of dopamine and 7. 5 percent sodium chloride infusion: experimental study in dogs with water restriction

JUSTIFICATIVA E OBJETIVOS: É controvertido o uso da infusão de dopamina na proteção renal. O objetivo desta pesquisa foi estudar o efeito da dopamina, da solução hipertônica e da associação de ambas em cães com restrição hídrica, simulando o jejum pré-operatório. MÉTODO: Foram estudados, em 32 cães anestesiados com tiopental sódico e fentanil, os seguintes parâmetros da função renal: fluxo plasmático efetivo renal (depuração de para-aminohipurato de sódio), ritmo de filtração glomerular (depuração de creatinina) e as depurações de sódio, de potássio e osmolar, excreção fracionária de sódio e potássio, excreção de sódio e potássio e a resistência vascular renal. Os parâmetros cardiovasculares foram: pressão arterial média, freqüência cardíaca, pressão da veia cava inferior, índice cardíaco, hematócrito e índice de resistência vascular periférica. Os animais foram subdivididos, através de sorteio, em 4 grupos experimentais: Grupo 1 - G1 (n = 8) - grupo controle; Grupo 2 - G2 (n = 8) infusão de dopamina (2 'g.kg-1.min-1), Grupo 3 - G3 (n = 8) solução de cloreto de sódio a 7,5 por cento (2 ml.kg-1) e Grupo 4 - G4 (n = 8) - associação de dopamina (2 'g.kg-1.min-1) e cloreto de sódio a 7,5 por cento (2 ml.kg-1). Os grupos tiveram quatro fases experimentais e cada momento com duração de 30 minutos, compreendendo os momentos M1, M2, M3 e M4. RESULTADOS: O grupo da dopamina (G2) apresentou diminuição da pressão arterial média, da resistência vascular renal e da excreção de potássio. O grupo da solução hipertônica de cloreto de sódio (G3) apresentou aumento do índice cardíaco, do volume urinário, da depuração de sódio e de potássio, da excreção urinária de sódio e potássio e da excreção fracionária de sódio...

BACKGROUND AND OBJECTIVES: Dopamine infusion for renal protection is controversial. This study aimed at observing the effects of dopamine, hypertonic solution and the association of both in dogs with water restriction, emulating preoperative fast. METHODS: The following renal function parameters were studied in 32 dogs anesthetized with sodium pentobarbital and fentanyl: effective renal plasma flow (sodium para-aminohippurate clearance), glomerular filtration rate (creatinine clearance), sodium, potassium and osmolar clearance, sodium and potassium fractional excretion and renal vascular resistance. Cardiovascular parameters were: mean blood pressure, heart rate, inferior vena cava pressure, cardiac index, hematocrit and peripheral vascular resistance index. Animals were randomly distributed in four experimental groups: Group 1 - G1 (n = 8) - control group; Group 2 - G2 (n = 8) - dopamine infusion (2 µg.kg-1.min-1); Group 3 - G3 (n = 8) - 7.5% sodium chloride (2 ml.kg-1) and Group 4 - G4 (n = 8) - association of dopamine (2 µg.kg-1.min-1) and 7.5% sodium chloride (2 ml.kg-1). Groups underwent four experimental stages lasting 30 minutes each, and involving moments M1, M2, M3 and M4. RESULTS: Dopamine group (G2) had mean blood pressure, renal vascular resistance and potassium excretion decrease. Hypertonic sodium chloride group (G3) had cardiac index, urinary volume, sodium and potassium clearance, sodium and potassium urinary excretion and sodium fractional excretion increase...

JUSTIFICATIVA Y OBJETIVOS: Es controvertido el uso de la infusión de dopamina en la protección renal. El objetivo de esta pesquisa fue estudiar el efecto de la dopamina, de la solución hipertónica y de la asociación de ambas en canes con restricción hídrica, simulando el ayuno pre-operatorio. MÉTODO: Fueron estudiados, en 32 canes anestesiados con tiopental sódico y fentanil, los siguientes parámetros de la función renal: flujo plasmático efectivo renal (depuración de para-aminohipurato de sodio), ritmo de filtración glomerular (depuración de creatinina) y las depuraciones de sodio, de potasio y osmolar, excreción fraccionaria de sodio y potasio, excreción de sodio y potasio y la resistencia vascular renal. Los parámetros cardiovasculares fueron: presión arterial media, frecuencia cardíaca, presión de la vena cava inferior, índice cardíaco, hematócrito e índice de resistencia vascular periférica. Los animales fueron subdivididos, a través de sorteo, en 4 grupos experimentales: Grupo 1 - G1 (n = 8) - grupo control; Grupo 2 - G2 (n = 8) infusión de dopamina (2 µg.kg-1.min-1), Grupo 3 - G3 (n = 8) solución de clorato de sodio a 7,5% (2 ml.kg-1) y Grupo 4 - G4 (n = 8) - asociación de dopamina (2 µg.kg-1.min-1) y clorato de sodio a 7,5% (2 ml.kg-1). Los grupos tuvieron cuatro partes experimentales y cada momento con duración de 30 minutos, comprendiendo los momentos M1, M2, M3 y M4. RESULTADOS: El grupo de la dopamina (G2) presentó diminución de la presión arterial media, de la resistencia vascular renal y de la excreción de potasio. El grupo de la solución hipertónica de clorato de sodio (G3) presentó aumento del índice cardíaco, del volumen urinario, de la depuración de sodio y de potasio, de la excreción urinaria de sodio y potasio y de la excreción fraccionaria de sodio...

Neuropharmacology of dopamine receptors: Implications in neuropsychiatric diseases

There has been an extraordinary recent accumulation of information concerning the neurobiology and neuropharmacology of dopamine [DA] receptors in the mammalian central nervous system. Many new DA molecular entities have been cloned, their gene, peptide sequences and structures have been identified, their anatomical distributions in the mammalian brain described, and their pharmacology characterized. Progress has been made toward developing selective ligands and drug-candidates for different DA receptors. The new discoveries have greatly stimulated preclinical and clinical studies to explore the neuropharmacology of DA receptors and their implications in the neuropathophysiology of different neuropsychiatric diseases including schizophrenia, Parkinson-s disease and attention- deficit hyperactivity disorder. Accordingly, it seems timely to review the salient aspects of this specialized area of preclinical neuropharmacology and its relevance to clinical neuropsychiatry

Efecto de las catecolaminas sobre la perfusión esplácnica en la sepsis / Effects of catecholamines on splanchnic perfusion in sepsis

Splanchnic ischemia is frequent in sepsis and septic shock and is related to impairment in intestinal permeability, derangement in mucosal barrier functions and translocation of proinflammatory mediators. These changes can contribute to the pathogenesis of multiple organ failure. Vasoactive drugs such as dobutamine and dopexamine can improve splanchnic perfusion and gastric intramucosal pH during sepsis. However, contradictory results have been obtained with dopamine and norepinephrine. On the other hand, epinephrine further impairs splanchnic perfusion. In view of the contradictory effects of different vasoactive drugs, gastric tonometry must be measured during their use, to find the optimal drug combination that optimizes splanchnic blood flow

Effects of flunarizine on dopamine dependent behaviours in rats.

1. Radio-ligand binding study has demonstrated that flunarizine has a high affinity for the rat striatal D 2 dopamine (DA) receptors. 2. In the present behavioural study conducted in rats it was observed that flunarizine, unlike the postsynaptic striatal D 2 DA receptor agonist apomorphine, did not induce stereotyped behaviour (SB) in rats. This indicates that flunarizine does not act as an agonist at the postsynaptic striatal D 2 DA receptors. 3. Flunarizine however, like the postsynaptic striatal D 2 DA receptor antagonist haloperiodal, inhibited the conditioned avoidance response, induced catalepsy and antagonized the SB induced by the DA agonists apomorphine and methamphetamine. 4. Our findings indicate that flunarizine acts as a postsynaptic striatal D 2 DA receptor antagonist.

Proteción renal en pacientes de cirugía cardíaca con disfunción renal pre-operatoria: dopamina vs presión de perfusión / Renal protection for patients with preoperative renal dysfunction undergoing cardiac surgery: dopamine vs perfusion pressure

Se estudiaron prospectivamente 17 pacientes con función renal preoperatoría alterada (creatininemia plasmática> 1,5 mg/dl) sometidos a cirugía con circulación extracorpórea. Los pacientes fueron randomizados a dos esquemas de protección renal. Grupo 1: Dopamina 2 ug/kg/min y grupo 2: Presión de perfusión elevada (70 mm Hg) durante circulación extracorpórea. Se midió filtración glomerular y flujo plasmático renal efectívo como clearances de inulina e 1251-hippuran, antes de la anestesia, durante la disección de la arteria mamaría, en circulación extracorpórea (hipotermia y normotermia), cierre del esternón y una hora del postoperatorío. Se midió además díuresís, electrolitos en sangre y orina, y clearances de creatinina, osmolar y de agua libre. La filtración glomerular durante la cirugía, antes de circulación extracorpórea, fue signifícativamente mayor en el grupo dopamina. Hubo tendencia a la disminución de la filtración glomerular durante la fase de hipotermia en ambos grupos. Por otra parte, el flujo plasmático renal efectivo aumentó discretamente respecto del control durante hipotermia en ambos grupos. Se encontró diferencias significativas entre ambos grupos durante cirugía, antes de circulación extracorpórea, en volumen urinario G1 (2,00 ñ 1,67 mL/min) vs G2 (0,29 ñ 0,19 mL/min), osmolaridad urinaria G1 (370 ñ 11 mL/min) vs G2 (627 ñ 157 mL/min), clearance osmolar G1 (2,15 ñ 1,42 mL/min) vs G2 (0,68 ñ 0,37 mL/mín), y potasio urinario G1 (33,1 ñ 12 mEq/L) vs G2 (71,1 ñ 23,7 mEq/L). Estos hallazgos sugieren un efecto de la dopamina sobre factores prerrenales en estos pacientes, ya que en los pacientes que no recibieron dopamina los valores encontrados son sugerentes de vasoconstricción renal

Empleo de inotrópicos en la sepsis: comparación de diferentes fármacos / Use of ionotropics in sepsis: comparison of different drugs

Objetivo: evaluar el empleo de diferentes fármacos inotrópicos y comparar los perfiles hemodinámicos, respiratorios y del metabolismo del oxígeno en una población de pacientes con sepsis y falla hemodinámica que requirieron el apoyo de uno o varios fármacos asociados. Diseño: se trata de un análisis retrospectivo mediante el estudio de las historias clínicas de 82 pacientes internados en el Centro de Tratamiento Intensivo del Hospital de Clínicas con diagnóstico de sepsis o shock séptico. Intervenciones y medidas: se efectuó un protocolo en el que se tuvieron en cuenta la edad, sexo, estadía, evolución, severidad mediante APACHE II, puntaje de Murray, existencia o no de shock, falla multiorgánica según W. Knaus, tipo de tratamiento: volumen (tipo, ml), fármacos utilizados (dosis, asociación) y la existencia o no de injuria pulmonar aguda o distrés según la Conferencia Consenso Americano Europea. En todos los pacientes se efectuó monitoreo hemodinámico pulmonar y sistémico con medidas del gasto cardíaco, obteniéndose 151 medias que corresponden a la monitorización para cada fármaco aislado o en combinación. Se definieron 10 grupos de pacientes según el tipo de fármaco. Análisis estadístico: los distintos valores hemodinámicos, respiratorios y del metabolismo del oxígeno se procesaron en un microprocesador PC AcerPower 333s en EPI INFO versión 5.0 a través del paquete estadístico Primer. Las variables se analizaron mediante análisis de varianza y test de Newman-Keuls. La diferencia de mortalidad se analizó con chi cuadrado. Se usó como nivel de significación una p menor de 0,05. Resultados: 56 por ciento de la población fue de sexo masculino, con una edad promedio de 46,02 ñ 18,97. La estadía promedio fue de 17 ñ 22 días. La mortalidad al alta del CTI fue de 63,4 por ciento. La severidad al ingreso mostró un APACHE II de 20,5 ñ 6,12. La mortalidad fue mayor a puntaje más elevado (X² p<0,05). No existieron diferencias entre los puntajes APACHE II de los 10 grupos de inotrópicos. El puntaje de injuria pulmonar (SIP) promedio de los pacientes con distrés respiratorio agudo del adulto (DRAA) fue de 2,63 ñ 0,48. La sepsis pulmonar con 39 por ciento seguida de la peritoneal con 24,4 por ciento y la genital con 13,4 por ciento fueron las más frecuentes. 39 por ciento de la población presentó shock séptico, la mortalidad ascendió a 90,6 por ciento siendo estadisticamente diferente (X², p<0,001)...

Dopaminergic drugs: pharmacological and therapeutic aspects / Drogas dopaminergicas: aspectos farmacológicos y terapéuticos

It has been widely established that dopamine and its agonists exect an import role in the regulation of the cardiovascular, renal hormonal systems, acting through adrenergic and beta-adrenergic systems. There are several DA-2 agonists such as bromocriptine pergolide, lisuride, and largotrile, which belong to the ergolin family and act both at central and peropheral levels-inhibiting norepinephrine release, which produces a decrease of arterial pressure and, in some cases, such as with bromocriptine and pergolide, a decrease in the heart rate. From a therapeutic viewpoint, the above mentioned DA-2 agonists are widely used for treating Parkinso's disease; these agonists act at the level of DA-2 receptors located in the nigrostriatal system. Bromocriptine and the other mentioned agonists DA-2 are used in the treatment of hyperprolatinemia and in pivitary tumors, since they decrease prolactin secretion and reduce the size of the tumor acting through inhibitory DA-2 receptors located in the tuberoinfuldibolar system. Similarly, there are Also DA-1 agonists such fenoldopam (selective) and piribedil non selective) which activate peripheral receptors, producing, a reduction of peripheral resistance and renal vascular resistance and an renal vascular resistance and an increase of renal blood flow. All these effects produce a decrease in arterial pressure and a reflex hearth rate increase. Fenoldopam in used in the treatment of arterial hypertensión, renal failure and heart failure. This agonist exerts its action at the level of the DA-1 receptors located in peripheral and renal resistance vessels (which leads to an increase use in renal blood flow and a decrease pressure). Among the selecttive antagonists of DA-2 receptors, we can mention metoclopramide and domperidone. Both antagonists produce a decrease in the hypotensor response of treatment of schizophrenia; it acts by activating DA-1 and DA-4 recepts located at the hypothalamus, olfactory bulb, and frontal cortex

Efeitos do propofol na resposta contrátil do miocárdio à dopamina e dobutamina: estudo experimental em coraçöes isolados de ratos / Effects of the propofol in the myocardial contractile response to dopamine and dobutamine: experimental study in rat's isolated heart

Objetivo: Estudo experimental das açoes farmacodinâmicas do propofol e sua interaçao com a dopamina e dobutamina em coraçoes isolados de ratos. Método: Foram estudadas as variaçoes da contratilidade miocárdica (dT/dt), em 30 coraçoes isolados de ratos. Em todos os animais, após anestesia por inalaçao de éter, os coraçoes foram excisados e perfundidos em sistema de Langendorff com soluçao de Krebs - Hensleit enriquecida com 95 por cento O2 e 5 por cento CO2, (pressao de 90 cm de H2O, temperatura constante de 37,O graus Celsius ñ O,5 graus Celsius). Foram estudados 30 animais divididos em: Grupo I (controle) - lO coraçoes perfundidos durante ll minutos com soluçao de Krebs - Hensleit; Grupo II (dopamina-propofol-dopamina) - lO coraçoes onde foram administrados dopamina (50 mcg/ml) e analisados os resultados nos 1(, 3( e 5( minutos e, posteriormente, propofol, (25 mcg/ml) infundindo-se l minuto após, dopamina (50 mcg/ml) e analisando-se os 1(, 3( e 5( minutos, Grupo III (dobutamina-propofoldobutamina) - diferiu do Grupo II pela substituiçao da dopamina por dobutamina (50 mcg/ml). Resultados: No Grupo I observou-se que a dT/dt variou de 39,57 ñ 3,97 (g.seg -l) a 39,37 ñ 3,44 (g.seg -1) (p>0,05) no período estudado. No Grupo II observou-se que, após a administraçao de propofol e dopamina, a dT/dt em (g.seg -l) apresentou queda de 17,61 por cento (pO,O5) no 1( minuto; 3,62 por cento (p>O,O5) no 3( minuto e 3,08 por cento (p>O,O5) no 5( minuto, comparado à injeçao isolada da dobutamina. Conclusao: O propofol (25 mcg/ml) nao alterou a resposta contrátil do miocárdio à dobutamina (50 mcg/ ml); no entanto, inibiu a resposta esperada pela açao da dopamina (50 mcg/ml) na contratilidade miocárdica.

Niveles de catecolaminas bajo el efecto del HEPB en diferentes regiones del SNC de ratón adulto: estudio preliminar / Preliminary study of the effect of HEPB on catecholamine levels in different regions of the brain

Diversos estudios han demostrado que la norepinefrina (NE) y la dopamina (DA) participan en la regulación del umbral convulsivo en diferentes modelos de epilepsia experimental a través de una estrecha relación entre la concentración y la predisposición para desarrollar crisis convulsivas. También, se ha demostrado que el mecanismo de acción de algunos anticonvulsionantes conocidos, se realiza bajo una regulación de la neurotransmisión a nivel sináptico. Por otro lado, los derivados de las butiramidas presentan una importante actividad anticonvulsionante en algunos animales de experimentación. Por lo que en el presente trabajo se investigó el efecto de un derivado de las butiramidas, la 4-hidroxi, 4-etil, 4-fenil butiramida (HEPB) sobre la concentración de NE y DA en diferentes regiones cerebrales como son: la corteza cerebral, el núcleo caudado y el hipocampo. Se utilizaron ratones adultos Balb/c tratados con solución salina fisiológica (testigo), propilenglicol al 10 por ciento como vehículo (testigo) y HEPB (experimental). Las regiones cerebrales se ontuvieron previa decapacitación de los animales y la concentración de NE y DA se realizó por cromatografía de líquidos de alta resolución con detección electroquímica. Los resultados muestran que el HEPB induce un incremento de NE (70 por ciento) en el núcleo caudado a la dosis de 20 mg/kg de peso corporal. Mientras que la DA sólo se incremento en 38 por ciento en esta misma región. En la corteza cerebral y el hipocampo no se encontró diferencia significativa respecto a los grupos testigo. Con estos resultados es difícil explicar el efecto del HEPB sobre el sistema catecolaminérgico en el núcleo caudado, no obstante, es necesario continuar con estudios complementarios que permitan precisar el posible mecanismo de acción del HEPB como anticonvulsionante y en particular su efecto sobre el transporte de DA en el núcleo caudado

Interaction of calcium channel blockers with different agonists in aorta from normal and diseased rats.

The interactions of calcium channel blockers (CCBs) with noradrenaline (NA), phenylephrine (PE), dopamine (DA) and KCl have been investigated in rat isolated aortic strip. In preparations from control and hypertensive (DOCA-saline) rats chronically treated with verapamil, nifedipine and diltiazem, there was partial inhibition of contractions to NA, PE and DA. However, with nimodipine, there was potentiation of responses. This could be related to the occurrence of different isoforms of L-type calcium channels. In preparations obtained from hyperthyroid rats the concentration-response curves of NA, PE and KCl were shifted to the right with depressed maximal response which could be secondary to the primary effect exerted on the heart. In preparations from L-thyroxine + nimodipine/nifedipine treated rats the concentration-response curves of NA, PE and KCl were shifted to the right and the maxima was depressed suggesting that this may be due to decreased alpha receptor density (NA and PE) and down-regulation of voltage operated channels (KCl).

Behavioural deactivations syndrome: abulia, hypodopaminergia and neuropsychologia

The current search to understand the neural substrate of goal- directed behaviour has created a new thrust of interest in unlocking the mystery behind those disorders that are characterized with poverty of thought and action. In this paper, various studies are reviewed to converge evidences that brain circuit rich in dopaminergic activity running from ventral tegmentum, and projecting in the nucleus accumbens and frontal cortex tend to produce abulia when its restitutive function fails. We will begin by examining consequences of dopamine agonism and Antagonism from preclinical studies as well as the inferences that can be made from studies in human. Then we discuss abulic features in neuropsychaiatric conditions, focusing on clinical manifestation, animal models, abnormal dopamine activity and pharmacological interventions

The beta-2 receptor plays a role in the hypotensive effect of L-Dopa

La levodopa ejerce efectos cardiovasculares tanto por conversasión a dopamina como por mecanismos no bien dilucidados. Los receptores beta adrenérgicos intervienen en los efectos de levodopa sobre el Sistema Nervioso Central. La participación de los receptores ß adrenérgicos en el efecto hipotensor periférico de la levodopa motiva el presente trabajo. En ratas anestesiadas (uretano 1 ml/100 i.p. y heparinizadas 300 U.I./Kgi.i.v.) se registró en un polígrafo la frecuencia cardíaca y la presión arterial media intracarotídea, una cánula traqueal facilitó la ventilación pulmonar. Los fármacos se inyectaron mediante un catéter de polietileno en la vena femoral. Grupos Experimentales: Grupo Control: a) Se estudió el efecto de Dopamina (3, 12 a 25µg/100gi.v.) y levodopa (12.5 a 100gi.v.) sobre presión arterial y frecuencia cardíaca. Pretratados con Beta bloqueadores: b) Se estudió la influencia de propranolol (50µg/100g), atenolol (100µg/100g) e ICI118.55(25µg/100g) inyectados 20 min antes sobre el efecto hipotensor de la dopamina y levodopa. La dopamina produjo hipotensión arterial dosis-dependiente (p<0.02) que no se modificó por propranolol, atenolol o ICI118.55. El tratamiento con atenolol no modificó la respuesta hipotensora de levodopa. El propranolol e ICI118.55 aumentaron la presión arterial. Propranolol e ICI118.55 comparten la propiedad de bloquear el receptor ß2. Se sugiere que ese receptor juega un rol fundamental en la hipotensión producida por levodopa