Ariel Gómez

Effects of p-chloro-phenylalanine on the behaviors induced by apomorphine and amphetamine in adult cats

1. The effects of serotonin depletion on the behaviors evoked by apomorphine or amphetamine are analyzed. Amphetamine (5 mg/kg, s.c.) or apomorphine (2 mg/kg, s.c.) were administered to fourteen adult mongrel cats. Inhibition of tryptophan hydroxylase was achieved by intraperitoneal injection of p-chlorophenylalanine (100 mg/kg daily for three consecutive days). Serotonin depleted animals were tested with either apomorphine or amphetamine (same doses as above). 2. Behaviors evoked by both drugs were recorded and quantified. The following behaviors were rated: motility (locomotion), alertness, fear, indifference, olfaction and lateral head movements. 3. Biochemical analysis of the raphe dorsalis and caudate nuclei of p-CPA treated animals showed an average drop in serotonin concentration of 77%. Serotonin depletion induced statistically significant changes in the following behaviors in amphetamine-treated cats: locomotion, fear, lateral head movements and alertness. Serotonin depleted cats tested with apomorphine showed significant changes only in olfaction and indifference behaviors. 4. Serotonin appears to play a significant modulatory role in some of the behaviors evoked by amphetamine, specially locomotion. Such role is less evident for the behaviors evoked by apomorphine.

Behavioral effects evoked by SKF 38393 and LY 171555 in adult cats

The aim of the present work was to study the behavioral effects elicited in adult cats by the selective D1 agonist, SKF 38393, and the D2 agonist, LY 171555, comparing their effects with those evoked by apomorphine. In 10 adult cats, 0.5, 1.0, 4.0, and 8.0 mg/kg IP of SKF 38393 were administered at random. A dose-response effect was observed related to alertness, indifference, and locomotion. The overall effect of SKF 38393 was inhibitory. To the same 10 animals, LY 171555 in doses of 0.25, 0.5, and 1.0 mg/kg were injected IP. This drug had an excitatory and more complex effect than what was observed with the D1 agonist. Increases in locomotion, in alertness, indifference, fear, olfaction, pupillary dilation, hallucination, limb flicking, and head shaking were recorded. Apomorphine given to the same cats, in a dose equimolar to 1.0 mg/kg of LY 171555, elicited behaviors that resembled those elicited by the latter drug, but of a lesser intensity and duration. The interval between the different treatments was approximately 2 months. These results show clearly that the D2 receptor is the main dopaminergic receptor involved in the mechanism of production of most of the behavioral effects produced by some of the dopaminergic agonist drugs like apomorphine.

Effects of SCH 23390 and sulpiride on the behaviors evoked by amphetamine and apomorphine in adult cats

1. The aim of the present study was to analyze whether the dopaminergic D1 and D2 receptors are involved in the production of the behaviors evoked by parenteral administration of amphetamine and apomorphine in adult cats. 2. Fifteen mongrel cats of both sexes were injected, in separate sessions, with 2.5 mg/kg of amphetamine and 2.0 mg/kg of apomorphine. The D1 receptor blocker, SCH 23390 was administered (0.3 mg/kg i.p.) and after 60 min, amphetamine and apomorphine were again injected on different days. The same procedure was carried on with sulpiride in two doses (20 and 30 mg/kg i.p.). The behaviors induced by the two dopaminergic drugs, before and after the receptor blocker administration were respectively compared. The Wilcoxon signed rank test was employed for statistical analysis. Three independent observers recorded the behaviors. 3. SCH 23390 and sulpiride produced per se hypomotility and sedation, effects that were considered when analysing the results. Some of the behaviors produced by amphetamine (pupillary dilation, head movements) were slightly modified by both receptor blockers. SCH 23390 only modified the licking behavior produced by apomorphine. In contrast, sulpiride blocked almost all the behaviors elicited by apomorphine, especially when the 30 mg/kg dose was administered. It is concluded that the behaviors produced by the 2 mg/kg dose of apomorphine are evoked by its binding to the post-synaptic dopaminergic D2 receptors and blocked by sulpiride.

Cholinergic blockade with scopolamine in adult cats. Effects on the behaviors evoked by apomorphine and amphetamine

1. The aim of this work is to analyse the role that the cholinergic system could play in the production of the behaviors evoked by apomorphine and amphetamine in adult cats. These two drugs were injected s.c. in separate sessions, before and after a s.c. administration of scopolamine which blocked the muscarinic receptors. The pre and post-scopolamine results of the behaviors produced by the two catecholaminergic drugs were compared using the non-parametric Wilcoxon signed rank test. 2. In a previous step a dose-response study of the behavioral effects of scopolamine, in doses of 0.05, 0.1, 0.4 and 0.8 mg/kg was carried out in ten cats. The Kruskal-Wallis and the non-parametric multiple comparison tests were employed. A dose-dependent decrease in motility (locomotion) and a dose-dependent increase in inappetence and pupillary dilation were found. 3. In thirteen cats which were injected with 2 mg/kg of apomorphine and 2.5 mg/kg of amphetamine the findings were: 1--apomorphine after scopolamine produced a decrease in the hypermotility, compared with the results observed with the former drug previous to scopolamine; 2--with amphetamine an increase in immobility and a decrease in indifference were observed. 4. The authors conclude that the decrease in motility recorded with apomorphine and amphetamine after scopolamine, could be attributed to the proper effect of scopolamine. No explanation could be found for the decrease in indifference found by injecting amphetamine after scopolamine. 5. Considering the antagonistic effect between the dopaminergic and the cholinergic systems and that the latter one has an arousal effect, we postulate that the behavioral indifference produced by apomorphine and amphetamine could be the result of a kind of blockade of the cholinergic system when the catecholaminergic system is activated through the administration of the two cited drugs.

Lidocaine reduces the hypoxia-induced release of an excitatory amino acid analog from rat striatal slices in superfusion

1. Lidocaine has been extensively investigated as a potential neuroprotective drug against ischemia-induced neurodegeneration without reaching any satisfactory conclusion. 2. The present work evaluates the effect of lidocaine -17 microM- on the hypoxia-induced release of tritiated D-aspartate from rat striatal slices in superfusion. 3. Hypoxia resulted in a significant increase in the amount of D-aspartate released from striatal slices preloaded with the tritiated excitatory amino acid analog. 4. The addition of lidocaine to the superfusion solution resulted in a drastic reduction in the amount of D-aspartate release evoked by hypoxia, rendering it close to normal values.

Effects of disulfiram, phenoxybenzamine and propranolol on the behaviors evoked by apomorphine and amphetamine in adult cats

The aim of this work was to study the role that the noradrenergic system could play in the mechanism of production of the behaviors evoked by parenteral injection of apomorphine and amphetamine in adult cats. Ten cats were injected s.c. with 2 mg/kg of apomorphine and 2.5 mg/kg of amphetamine in separate sessions. The behaviors were recorded, until control conditions were again attained. In a second stage, disulfiram was administered ip., followed by apomorphine and amphetamine in the same doses as cited above. The effects on behaviors produced by disulfiram and those of apomorphine and amphetamine were recorded by three independent observers. Comparisons of the pre- and post-disulfiram behavioral results were analyzed with the help of the non-parametric Wilcoxon signed rank test. In another group of ten cats a similar procedure was carried on employing the alpha and beta noradrenergic blocking agents, phenoxybenzamine and propranolol. The noradrenergic blocking drugs, especially disulfiram and phenoxybenzamine produced by themselves a decrease in motility, in alertness and an increase in indifference and inappetence. Apomorphine and amphetamine administered after the blocking drugs showed slight behavioural modifications, reflection most of them the changes produced by the three blocking drugs. It is concluded that probably the nor-adrenergic system could be involved in the hypomotility elicited by amphetamine. NA is not involved in the induction of the other behaviors evoked by apomorphine and amphetamine.

Diagnóstico precoz de enfermedad de Parkinson: neurospect del transportador de Dopamina

Antecedentes. Hemos comunicado recientemente que NeuroSPECT (NSP) del Transportador de Dopamina (DAT) es un metodo altamente sensible para el diagnostico precoz de enfermedad de Parkinson (26). Objetivos. Evaluar la Sensibilidad de NSP de DAT en pacientes de hemiparkinsonismo de novo y comparar los resultados contralaterales VS. Ipsilaterales al lado sintomatico, asi como la comparacion con voluntarios sanos y evaluar asi la sensibilidad para detectar alteraciones pre-sintomaticas y tambien las sintomaticas. Material y metodo. El presente estudio se refiere a 20 pacientes con hemiparkinsonismo de novo(HP) (UPDRS V =1) de 3.0 anos promedio de evolucion y 60.3 anos de edad; siendo 5/20 mujeres; el UPDRS III promedio era 14, 8 HP izquierdo y 12 HP, derecho. Se comparan con 28 individuos normales, 21/28 mujeres, con edad promedio 54 anos. Se obtuvo imagenes tridimensionales mediante NST con 30 mCI del radiofarmaco TRODAT-1 Tc99m, cuatro horas despues de la inyeccion intravenosa. Resultados. En controles se observa maxima distribucion del DAT en el caudado y putamen. Establecemos comparacion con corteza occipital, que presenta minima concentracion no especifica de DAT. En 20 pacientes con HP se observo disminucion significativa de la concentracion de DAT en comparacion con la referencia cortical; esta anormalidad era bilateral con predominio en el nucleo contralateral al lado sintomatico. La sensibilidad del Putamen para detectar Enfermedad de Parkinson es de 90% y la Especificidad es de 91%. En los controles normales se observo en 25 de los 28 pacientes un aumento marcado de la concentracion de DAT en los nucleos caudado y putamen en comparacion con la corteza de referencia. Conclusion. La elevada sensibilidad de TRODAT 99m NeuroSPECT en pacientes con diagnostico de enfermedad de Parkinson sintomatico se manifiesta ademas por demostrar precozmente anormalidades en el estriado contralateral al lado sano aunque de menor magnitud, vale decir, en estado presintomatico

Comparative analysis of the behaviors evoked by bromocriptine and quinpirole (LY 171555) in adult cats

The aim of this work was to compare the behavioral effects of bromocriptine and quinpirole, two agonists of the D-2 dopaminergic receptor, either injected alone or combined with the D-1 dopaminergic receptor, SKF 38393. In ten adult mongrel cats the following experimental series were carried out: i) a dose-response study with bromocriptine administering 0.5-1.0-4.0 and 8.0 mg/kg s.c.; ii) a behavioral study injecting 4.0 mg/kg of bromocriptine plus 2.0 mg/kg of SKF 38393; iii) the same analysis administering 0.5 mg/kg of LY 171555 plus 1.0 mg/kg of SKF 38393, compared with the same dose of LY 171555 plus 4.0 mg/kg of SKF 38393; iv) an analysis of the behavioral effects of 8.0 mg/kg of bromocriptine compared with 1.0 mg/kg of quinpirole. The main findings were: i) bromocriptine injected, in four different doses evoked decrease in locomotion, and increase in indifference, inappetence, pupillary dilation and limb flicks; ii) the combined administration of 4.0 mg/kg of bromocriptine plus 2.0 mg/kg of SKF 38393 did not elicit behavioral changes different to those produced by bromocriptine alone; iii) quinpirole (1.0 mg/kg) evoked more intense behaviors than bromocriptine (8.0 mg/kg); iv) comparing quinpirole injected alone with the combination of quinpirole plus SKF 38393, this latter treatment produced more intense behaviors than the former. It is concluded: i) SKF 38393 potentiates the behavioral effects produced by quinpirole; this potentiation was not found when bromocriptine was combined with SKF 38393 and ii) the more intense behavioral effect elicited by quinpirole compared with bromocriptine may be explained by the fact that the latter drug is a selective D-2 agonist, whereas the former one is an agonist of the D-2 and the D-3 receptors.