Schedule-induced polydipsia is associated with increased spine density in dorsolateral striatum neurons.

Schedule-induced polydipsia (SIP) is an adjunctive behavior in which rats exhibit excessive drinking as a consequence of intermittent feeding, and it has been proposed as a candidate model to study the development of compulsive and repetitive behavior. Although several brain structures are involved in compulsive behavior, it has been suggested that alterations in fronto-striatal circuits may underlie compulsive spectrum disorders. In the present work, we examined whether SIP would induce modifications in dorsolateral striatum (DLS) and anterior prefrontal cortex (aPFC) neurons. Specifically, the effects of 20 sessions of SIP were determined in the dendrites of DLS medium spiny neurons and in the basal dendritic arbors of layer V pyramidal cells in the aPFC. The structure, size and branching complexity in aPFC neurons were also studied. Results showed that SIP resulted in an increase in dendritic spine density in DLS neurons. Moreover, dendritic spine density was highly correlated with the level of drinking in animals subjected to SIP. By contrast, we observed no differences either in dendritic spine density or in the morphological structure of the dendrites of the aPFC in SIP rats compared to their control counterparts. We hypothesize that SIP-induced structural plasticity in DLS neurons could be related to inflexible response in compulsive behavior. The findings of this study could provide new insights into the involvement of particular cell populations of the dorsolateral striatum and anterior prefrontal cortex regions in compulsive spectrum disorders.

Usefulness of addition of CT perfusion to CT angiography for brain death diagnosis in a child.

CT perfusion is a new technique that is rapid, available and minimally invasive which provides functional vascular information and can be made after conventional CT and CT angiography at the same imaging session. CT perfusion applications have focused on ischemic stroke with only a short series of applications to brain death diagnosis. Instead, CT angiography is frequently performed as a confirmatory test of brain death, but it has not been completely validated yet. Hence CT perfusion may help in supporting the diagnosis of brain death. We present the case of a 12-year-old child with clinical criteria for brain death who required a confirmatory test. CT angiography and CT perfusion were performed. Both revealed the absence of any intracranial blood flow which supported the clinical diagnosis of brain death.

Molecular descriptor based on a molar refractivity partition using Randic-type graph-theoretical invariant.

PURPOSE: Development of a novel semi-empirical descriptor (MR(chi) for molecular modelling. METHOD: The index is based on a molar refractivity partition using Randictype graph-theoretical invariant. RESULTS: This hybrid index describes not only the London dispersive forces in a ligand fragment related to the molar refractivity but also structural features of the molecule It is also applicable in Quantitative Structure-Activity Relationship (QSAR) and Quantitative Structure-Property Relationship (QSPR) studies. CONCLUSIONS: The method is convenient and can discriminate between isomers.

Antipunishment effects of diazepam on two levels of suppression of schedule-induced drinking in rats.

Food-deprived Wistar rats were exposed to a fixed-time (FT) 60-s food delivery schedule until they developed schedule-induced drinking. Rats were matched in pairs according to their licking rates and were designated master or yoked at random. Every fifth lick by master rats was followed by an electric shock during two signalled 5-min periods, which ran concurrently with the food delivery schedule. For the master rats, shock intensities were adjusted to reduce licking to 5-30% (low suppression) or 50-75% (high suppression) of the unpunished licking rates. Yoked rats received the same shocks as master rats, but independently of their own licking. The drinking by yoked animals was not decreased by the presentation of these lick-independent shocks. Diazepam (0.3-10.0 mg/kg) was studied for its effects on punished and nonpunished schedule-induced drinking. Intermediate doses of the drug increased the punished behavior of master rats, but only when schedule-induced drinking was highly suppressed. Diazepam dose dependently decreased licking rates in all other conditions. The antipunishment effects of benzodiazepines may depend on the level of suppression of schedule-induced drinking, and this is in keeping with the results of other experimental preparations where behavior was under aversive control.

Síntesis de derivados del ácido cinámico bajo irradiación de microondas en ausencia de disolventes / Synthesis of deriving of the sour cinámic under irradiation of microondes in absence of solvent

En recientes años se ha incrementado el interés por la aplicación de la radiación de las microondas a la síntesis orgánica, esto ha sido motivado por la influencia reportada de ésta, sobre la velocidad de la reacción, incremento de la pureza y el rendimiento de los productos, y la posibilidad de trabajar sin emplear disolventes. Los ácidos cinámicos son una importante familia de compuesto reportados en la obtención de principios bioactivos y anticorrosivos, así como intermediarios de procesos químicos, como por ejemplo en la síntesis de estirenos. La síntesis de éstos se ha realizado por métodos convencionales, sometiendo los reactivos a calentamientos prologados con el empleo de varios catalizadores básicos y largos tiempos de reflujo. En nuestro trabajo reportamos la síntesis de derivados de aril sustituidos del ácido cinámico bajo irradiación de micoondas. Se efectuo la reacción empleando soportes sólidos minerales como catalizadores básicos. Los rendimientos alcanzados son altos, en cortos tiempos de reacción y productos de alta pureza

Effects of d-amphetamine, diazepam and buspirone on schedule-induced polydipsia suppressed by response-dependent and response-independent shock.

Food deprived Wistar rats were exposed to a fixed time 60 s food schedule until they developed schedule-induced polydipsia. Rats were matched in pairs according to their licking rate, being designated experimental or yoked control at random. Every fifth lick by experimental rats was then followed by an electric shock (0.05, 0.1, or 0.2 mA) while the food schedule continued in operation. Yoked-control rats received the same shocks as experimental rats, but independently of their own licking. Drugs were then tested on the suppressed rates of licking. Diazepam (0.5-2.0 mg/kg) increased punished schedule-induced polydipsia, a result not observed in yoked controls. No increases in the licks per minute of experimental or control animals were found after d-amphetamine (0.25-4.0 mg/kg) or buspirone (0.5-8.0 mg/kg). In comparison with previous results it is concluded that the antipunishment effects of drugs on schedule-induced behaviour depend on the type of punishment contingency.

Effects of d-amphetamine on temporal distributions of schedule-induced polydipsia.

Food-deprived rats were divided into four groups according to the equal interval and time durations of a multiple fixed-interval, fixed-time schedule (15, 30, 60, and 120 s). Fixed-time components were signaled by a tone and lever withdrawal. d-Amphetamine (0.25-4.0 mg/kg) produced similar dose-dependent reductions in the drinking and licking induced by fixed-interval and fixed-time schedules. These dose-dependent decrements were a function of the interfood interval length. More licks occurred early in the interfood intervals with doses of d-amphetamine. Dose-dependent shifts to the left were observed in the distribution of licking, and there were dose-dependent decreases in the quarter-life, which were a function of fixed-interval and fixed-time lengths. The maximum lick rate within interfood intervals occurred at about the same absolute time in schedules up to 60 s; therefore, the effects of d-amphetamine were not mediated by its effects on temporal discrimination.

Food deprivation and food-delay effects on the development of adjunctive drinking.

Twelve rats were food-deprived to 90% or 70% of their free-feeding weights. Food pellets were then delivered every 60 s (Fixed Time 60-s schedule), and the development of adjunctive drinking was measured by the water consumed and the number of licks. For "master" rats, each lick was followed by 10-s delays in food delivery. Yoked control rats received food at the same time as their master rats and independently of their own behavior. At 70% deprivation, both master and control rats developed similar levels of schedule-induced licking, but the master rats drank less water. At 90% deprivation, master animals showed little drinking and licking, but the development of adjunctive drinking was not completely prevented. Drinking by yoked control rats did not differ as a function of deprivation level. In showing that lick-dependent delays in food delivery reduce the asymptotic development of adjunctive drinking as a function of the rats' level of food deprivation, these results support the view that environmental influences on schedule-induced drinking are modulated by motivational factors.

Síntesis de derivados del ácido cinámico bajo irradiación de microondas en ausencia de disolventes / Synthesis of deriving of the sour cinámic under irradiation of microondes in absence of solvent

En recientes años se ha incrementado el interés por la aplicación de la radiación de las microondas a la síntesis orgánica, esto ha sido motivado por la influencia reportada de ésta, sobre la velocidad de la reacción, incremento de la pureza y el rendimiento de los productos, y la posibilidad de trabajar sin emplear disolventes. Los ácidos cinámicos son una importante familia de compuesto reportados en la obtención de principios bioactivos y anticorrosivos, así como intermediarios de procesos químicos, como por ejemplo en la síntesis de estirenos. La síntesis de éstos se ha realizado por métodos convencionales, sometiendo los reactivos a calentamientos prologados con el empleo de varios catalizadores básicos y largos tiempos de reflujo. En nuestro trabajo reportamos la síntesis de derivados de aril sustituidos del ácido cinámico bajo irradiación de micoondas. Se efectuo la reacción empleando soportes sólidos minerales como catalizadores básicos. Los rendimientos alcanzados son altos, en cortos tiempos de reacción y productos de alta pureza

Food-deprivation effects on punished schedule-induced drinking in rats.

Food-deprived rats (at 80% of their free-feeding weights) were exposed to a fixed-time 60-s schedule of food-pellet presentation and developed schedule-induced drinking. Lick-dependent signaled delays (10 s) to food presentation led to decreased drinking, which recovered when the signaled delays were discontinued. A major effect of this punishment contingency was to increase the proportion of interpellet intervals without any licks. The drinking of yoked control rats, which received food at the same times as those exposed to the signaled delay contingency (masters), was not consistently reduced. When food-deprivation level was changed to 90%, all master and yoked control rats showed decreases in punished or unpunished schedule-induced drinking. When the body weights were reduced to 70%, most master rats increased punished behavior to levels similar to those of unpunished drinking. This effect was not observed for yoked controls. Therefore, body-weight loss increased the resistance of schedule-induced drinking to reductions by punishment. Food-deprivation effects on punished schedule-induced drinking are similar to their effects on food-maintained lever pressing. This dependency of punishment on food-deprivation level supports the view that schedule-induced drinking can be modified by the same variables that affect operant behavior in general.

Food-delay duration and the development of schedule-induced polydipsia in rats.

Twelve rats were exposed to a schedule that delivered a food pellet every 60 s (fixed time 60 s). The development of schedule-induced polydipsia was measured in terms of the water consumed and the licks per interpellet interval. Every lick by master rats initiated an unsignalled delay of 2 or 50 s in food delivery. Yoked-control rats received food at the same time as their masters, being unaffected by their own licking. Schedule-induced polydipsia developed in master rats exposed to 2-s delays, but more slowly and to a lesser extent than control animals. The development of polydipsia was prevented in master rats exposed to 50-s delays, however. When these delays were discontinued, polydipsia was obtained by master rats. The finding that the effect of the delays was modulated by their duration supports the view that the development of schedule-induced polydipsia is sensitive to control by its environmental consequences.

Pharmacological analysis of the scratching produced by dopamine D2 agonists in squirrel monkeys.

Several dopamine agonists, administered i.m., produced persistent, excessive and non-localized scratching in squirrel monkeys (Saimiri sciureus). Studies were conducted with a series of drugs to determine the pharmacological mechanisms responsible for this effect. All of the dopamine D2 agonists studied produced dose-related increases in scratching, whereas several dopamine D1 receptor agonists, indirect dopamine agonists and drugs acting on other receptors failed to produce dose-related increases in scratching. The scratching produced by D2 agonists was stereospecific; (-)-NPA produced scratching whereas its (+)-enantiomer was inactive up to doses 300-fold higher. Scratching induced by quinpirole was attenuated by both D2 and D1 antagonists, and this antagonism was stereospecific, with the D2 antagonist (-)-eticlopride, but not its enantiomer, active. Sensitivity developed to the effects of D2 agonists with the quinpirole dose-effect curve shifting to the left by a factor of approximately 64. Two partial D2 receptor agonists (SDZ 208-911 and SDZ 208-912) had limited efficacy in producing scratching, however, one partial D2 receptor agonist (terguride) was fully efficacious, suggesting that there are spare receptors for this effect. The peripherally active dopamine antagonist domperidone and the histamine antagonist diphenhydramine also reduced the scratching induced by D2 agonists, but not to the same extent as centrally acting D2 antagonists. Scratching in squirrel monkeys is an effect that appears to be due to agonist actions at D2 receptors, and may be mediated by a release of histamine. This behavioral activity may be useful as an in vivo indication of D2 receptor activity in primates.

Rate-dependency hypothesis and the rate-decreasing effects of d-amphetamine on schedule-induced drinking.

The high levels of drinking induced by intermittent food-reinforcement schedules are dose-dependently reduced by acute doses of d-amphetamine. The present study evaluated whether the effects of d-amphetamine on this schedule-induced drinking reflect the reduction of high rates of responding. Twenty-four rats were divided into six groups (n = 4) according to the interval and time durations of a multiple fixed-time (FT) fixed-interval (FI) schedule (15s, 30s, 60s, 120s, 240s and 480s). FT components were signalled by a tone and by lever withdrawal. Doses of 0.25 to 4.0mg/kg of d-amphetamine were administered i.p. 10min before test sessions. d-amphetamine produced similar dose-dependent reductions in rate of licking induced by FT and FI schedules. Rate-decreasing effects on operant lever pressing were also found after administrations of d-amphetamine. The dose-dependent decrements produced by d-amphetamine were a function of the inter-food interval length in both schedule-induced and operant behaviours. These rate-decreasing effects were rate-dependent, but d-amphetamine interacted differentially with control rates of adjunctive and operant behaviours, causing a greater suppression of the lower rates of adjunctive licking and the higher rates of operant lever pressing.

Effects of drugs on the temporal distribution of schedule-induced polydipsia in rats.

Drinking was induced in food-deprived rats by a fixed-time 1-min schedule of food presentation. With three rats, d-amphetamine (0.25, 0.5, 1.0, and 2.0 mg/kg) led to a dose-related increase in licking early in the interfood intervals, the peak of the temporal distribution of licking being shifted to earlier values. These effects were seen even when d-amphetamine had no effect on overall rates of licking and drinking. With another three rats, however, diazepam (0.5, 1.0, 2.0, and 4.0 mg/kg) did not shift the peak of the temporal distribution of licks in interfood intervals, even at doses that produced small increases in overall rates of licking and drinking. However, diazepam did reduce the peak of the distributions of licks at doses that did not decrease water intake and licks per minute.

Hepatoprotective effects of lobenzarit disodium on acetaminophen-induced liver damage in mice.

We have studied the effects of the immunomodulator drug lobenzarit in the model of acute hepatotoxicity induced by a high oral dose (600 mg/kg) of acetaminophen in mice. Lobenzarit at doses of 25, 50 and 100 mg/kg i.p. decreased significantly the activity of alanine aminotransferase in serum, which was increased by acetaminophen alone, and increased the concentration of reduced glutathione in mice liver, which is depleted by acetaminophen. Lobenzarit also reduced liver damage induced by acetaminophen in mice, which was observed by electron microscopy. The hepatoprotective effects of lobenzarit were dose-dependent and they were produced when lobenzarit was administered 30 min before acetaminophen or 2 and 4 h after it. It is concluded that lobenzarit exerts some effects which resemble those of an antidote of acetaminophen such as N-acetylcysteine.

Effects of d-amphetamine and of diazepam on non-punished and punished schedule-induced drinking in rats.

Drinking induced in food-deprived rats by a Fixed-Time 1min schedule of food presentation was measured by the amount of water consumed per session and the number of licks per inter-food interval. Subsequently each lick initiated a 10-sec signalled delay in the delivery of food, which led to a decrease in drinking (punishment). With three rats the effects of d-amphetamine (0.25, 0.5, 1.0, 2.0mg/kg) were assessed on non-punished and then on punished drinking. With another three rats, the effects of diazepam (0.5, 1.0, 2.0, 4.0mg/kg) were assessed. The smaller doses of d-amphetamine had no consistent effect on overall measures of non-punished schedule-induced drinking, but the largest dose decreased them. With the signalled delay d-amphetamine increased punished schedule-induced drinking. Non-punished drinking was increased by small doses of diazepam and decreased by the largest dose, but no dose of diazepam affected punished drinking.

Propiedades hepatoprotectoras del Lobenzarit disódico en la rata / Hepatoprotective properties of disodium Lobenzarit in the rat

El nuevo medicamento antirreumático Lobenzarit disódico, ha sido evaluado por nosotros para esclarecer si posee también propiedades hepatoprotectoras. Utilizando el modelo experimental de hepatotoxicidad aguda en ratas inducida por el Cl4C, hemos encontrado que el Lobenzarit a las dosis de 50 y l00 mg/kg de peso, administrado por vía intraperitoneal disminuye considerablementeel daño hepático inducido por el Cl4C, lo que se evidencia por una reducciónsignificativa de la actividad de la ALAT sérica y de los triglicéridos en el hígado , hasta alcanzarse concentraciones prácticamente normales de éstos. El Lobenzarit también disminuye considerablemente las lesiones inducidas por el Cl4C en este órgano, lo que detectamos por microscopía electrónica. Nuestros resultados evidencian que el Lobenzarit posee propiedades hepatoprotectoras en el modelo experimental utilizado. (AU)

Propiedades hepatoprotectoras del Lobenzarit disódico en la rata / Hepatoprotective properties of disodium Lobenzarit in the rat

El nuevo medicamento antirreumático Lobenzarit disódico, ha sido evaluado por nosotros para esclarecer si posee también propiedades hepatoprotectoras. Utilizando el modelo experimental de hepatotoxicidad aguda en ratas inducida por el Cl4C, hemos encontrado que el Lobenzarit a las dosis de 50 y l00 mg/kg de peso, administrado por vía intraperitoneal disminuye considerablementeel daño hepático inducido por el Cl4C, lo que se evidencia por una reducciónsignificativa de la actividad de la ALAT sérica y de los triglicéridos en el hígado , hasta alcanzarse concentraciones prácticamente normales de éstos. El Lobenzarit también disminuye considerablemente las lesiones inducidas por el Cl4C en este órgano, lo que detectamos por microscopía electrónica. Nuestros resultados evidencian que el Lobenzarit posee propiedades hepatoprotectoras en el modelo experimental utilizado.

The effects of signalled and unsignalled lick-dependent delays on the development of schedule-induced drinking in rats.

Food pellets were programmed to be delivered to rats every 60 sec (Fixed Time 60-sec schedule), and the development of schedule-induced drinking was measured in terms of the amount of water consumed and the number of licks per inter-pellet interval. For some rats (masters) 10-sec delays in food delivery were dependent on licks. Yoked-control rats received food at the same time as their masters and independently of their own behaviour. In Experiment 1, in which the delays were signalled by a blackout, the master rats began to drink, but this schedule-induced behaviour then decreased to levels lower than those shown by the yoked controls. When the signalled delays were discontinued, the drinking of the master rats recovered. In Experiment 2, in which the delays were not signalled, the master rats did not develop as much schedule-induced drinking as the yoked controls, and discontinuing the delays led to only small increases in drinking. These results support the view that schedule-induced drinking is subject to control by its consequences.

Punishment of schedule-induced drinking in rats by signaled and unsignaled delays in food presentation.

Food-deprived rats were exposed to a fixed-time 60-s schedule of food-pellet presentation and developed schedule-induced drinking. Using an ABA reversal design, three experiments investigated the effects of events then made dependent on licks. In Experiment 1, lick-dependent signaled delays (10 s) in food presentation in general led to decreased drinking, which recovered when the signaled delays were discontinued. The drinking of yoked-control rats, which received food at the same times as those exposed to the signaled-delay contingency, showed much smaller changes. Experiment 2 showed that 10-s lick-dependent signals alone did not reduce drinking. In Experiment 3, when licks produced unsignaled 10-s delays in food there were less marked and more gradual changes in drinking than in Experiment 1, although these effects again were greater than with yoked-control animals. We concluded that both signaled and unsignaled delays functioned as punishers of drinking. These findings support the view that schedule-induced drinking, like operant behavior, is subject to control by its consequences.