Impairment of locomotor activity induced by the novel N-acylhydrazone derivatives LASSBio-785 and LASSBio-786 in mice

The N-acylhydrazone (NAH) analogues N-methyl 2-thienylidene 3,4-benzoylhydrazine (LASSBio-785) and N-benzyl 2-thienylidene 3,4-benzoylhydrazine (LASSBio-786) were prepared from 2-thienylidene 3,4-methylenedioxybenzoylhydrazine (LASSBio-294). The ability of LASSBio-785 and LASSBio-786 to decrease central nervous system activity was investigated in male Swiss mice. LASSBio-785 or LASSBio-786 (30 mg/kg, ip) reduced locomotor activity from 209 ± 26 (control) to 140 ± 18 (P < 0.05) or 146 ± 15 crossings/min (P < 0.05), respectively. LASSBio-785 (15 or 30 mg/kg, iv) also reduced locomotor activity from 200 ± 15 to 116 ± 29 (P < 0.05) or 60 ± 16 crossings/min (P < 0.01), respectively. Likewise, LASSBio-786 (15 or 30 mg/kg, iv) reduced locomotor activity from 200 ± 15 to 127 ± 10 (P < 0.01) or 96 ± 14 crossings/min (P < 0.01), respectively. Pretreatment with flumazenil (20 mg/kg, ip) prevented the locomotor impairment induced by NAH analogues (15 mg/kg, iv), providing evidence that the benzodiazepine (BDZ) receptor is involved. This finding was supported by the structural similarity of NAH analogues to midazolam. However, LASSBio-785 showed weak binding to the BDZ receptor. LASSBio-785 or LASSBio-786 (30 mg/kg, ip, n = 10) increased pentobarbital-induced sleeping time from 42 ± 5 (DMSO) to 66 ± 6 (P < 0.05) or 75 ± 4 min (P < 0.05), respectively. The dose required to achieve 50% hypnosis (HD50) following iv injection of LASSBio-785 or LASSBio-786 was 15.8 or 9.5 mg/kg, respectively. These data suggest that both NAH analogues might be useful for the development of new neuroactive drugs for the treatment of insomnia or for use in conjunction with general anesthesia.

Aspectos moleculares de la resistencia a insecticidas / Molecular basic of insecticide resistance

El surgimiento de resistencia en poblaciones de insectos es uno de los efectos indeseables asociados al uso de insecticidas, y es un buen ejemplo del modo en que ocurren los procesos microevolutivos. En 1908 se documentó por primera vez la existencia de insectos resistentes a insecticidas. Ahora se conocen casos de resistencia en más de 500 especies de artrópodos. Los principales mecanismos que confieren resistencia a insecticidas son penetración cuticular reducida, metabolismo degradativo aumentado y reducción en la susceptibilidad de los sitios de acción. Los métodos de la biología molecular permiten identificar las bases moleculares de esos mecanismos. El propósito de este artículo es reseñar el conocimiento disponible acerca de la biología molecular de la resistencia a insecticidas: mutaciones puntuales en genes de acetilcolinesterasa (Drosophila melanogaster) y del receptor de GABA (varias especies), inserciones en genes de transferasas (D. melanogaster) y del citocromo P450 (D. melanogaster), amplificación de genes de esterasas (Myzus persicae y Culex pipiens / quinquefasciatus complex), cambios que afectan la expresión del gen del citocromo P450 (Musca domestica), y una mutación ligada al gen del canal de sodio dependiente de voltaje (M. domestica)

Alcoolismo e benzodiazepínicos / Alcoholism and benzodiazepine

Com o intuito de estudar a açao e os efeitos dos benzodiazepínicos no tratamento do alcoolismo, foi realizado um levantamento bibliográfico sobre o assunto, com destaque para a açao do álcool e dos benzodiazepínicos no SNC, mais especificamente no sistema gabaérgico. Fazendo-se uma correlaçao farmaco-clínica, constatou-se que as síndromes de abstinência, que variam de leves a severas, como delirium tremens, sao tratadas com diversas dosagens de benzodiazepínicos obtendo-se bons resultados. Nao foi necessária, na maioria dos pacientes, a associaçao com outras drogas depressoras e sedativas.

Role of the amygdala, hippocampus and entorhinal cortex in memory consolidation and expression

1. Experiments using localized microinfusions of specific agonists and antagonists of neurotransmitter receptors have shown that the amygdala, hippocampus, medial septum and entorhinal cortex are involved in memory consolidation, storage and expression. The data are consistent with observations derived from lesion studies suggesting a role for these structures in memory processes, but permit many additional conclusions concerning the mechanisms involved and their timing. 2. Memories are initially processed by glutamatergic N-methyl-D-aspartate (NMDA) receptors in amygdala, hippocampus and medial septum, which are sensitive to amino-phosphono valerate (AP5). Memory of inhibitory avoidance is processed by the three structures; memory of habituation to a novel environment is processed only by the hippocampus. At the time of consolidation, immediately after training, gamma-aminobutyrate type A (GABA-A) receptors, modulated by endogenous benzodiazepines, play an inhibitory role, and cholinergic muscarinic and beta-noradrenergic transmission play a modulatory role. 3. From 90 to 180 min after training, memories are blocked by cyano-nitro-quinoxalinedione (CNQX) given into the amygdala, septum and hippocampus. CNQX blocks non-NMDA glutamatergic receptors. Also between 90 and 180 min after training, memory of the habituation and inhibitory avoidance tasks is blocked by the infusion of AP5 or of the GABA-A agonist, muscimol, into the entorhinal cortex. This late post-training intervention of the entorhinal cortex is essential for the integration of successively acquired memories, and occurs in response to the simultaneous activation of CNQX-sensitive synapses in amygdala and hippocampus. 4. The expression of memory is blocked by the infusion of CNQX, at the time of testing, into the amygdala and hippocampus (inhibitory avoidance), into the hippocampus but not the amygdala (habituation), or into the entorhinal cortex (for the two tasks). Since consolidation is blocked by AP5 infused into these structures (see above), the data agree with the hypothesis that memories are mediated by (or actually consist of) long-term potentiation (LTP) in these areas of the brain. LTP induction is blocked by AP5 and LTP expression is blocked by CNQX. It is possible that, at the time of memory expression, the entorhinal cortex is an output of the amygdala and hippocampus

Estudo da açäo do suco extraído das folhas de Bryophyllum calycinum salisb (Crassulaceae) sobre o sistema digestivo / Study of the action of the juice extracted from Bryophyllum calycinum salisb (Crassulaceae) on the gabaergic system

Bryophyllum calycinum Salisb. (Crassulaceae) é uma planta largamente utilizada em regiöes tropicais e subtropicais. Seu principal uso consiste como uma medicaçäo tópica em afecçöes cutâneas de natureza alérgica. (NASSIS, 1991) (16) demonstrou ser o suco extraido desta planta um potente antagonista dos receptores H-1 a nível periférico em ratos. Um trabalho subsequente (NASSIS et al, 1991) (17) mostrou que o suco extraído da Crassulaceae tem uma depressora no SNC. O presente estudo teve por objetivo a investigaçäo de uma eventual açäo GABAérgica do suco. A partir dos resultados obtidos pudemos concluir que o suco näo apresenta atividade sobre o sistema GABAérgico

Effect of post-training injections of flumazenil into the amygdala, hippocampus and septum on retention of habituation and of inhibitory avoidance in rats

Adult rats were submitted to two different behavioral tasks using the same apparantus: the habituation of exploration of the apparatus considered as a novel environment as measured by the decrease in number of reaings and of ambulation between training and testing, and step-down inhibitory avoidance as measured by the increase in the latency to step down from a start platform into an electrified grid between the training and the test session.The training-test interval for both tasks was 20 h.The immediate post-training injection of the benzodiazepine receptor antagonist flumazenil (10 nmol) bilateral into the hippocampus enhanced retention of the two tasks.Application of the same drug, at the same dose to the septum or amygdala had no effect on habituation but enhanced retention of the avoidance task. The data are consistent with previous findings showing that both tasks are accompanied by the release of benzodiazepine like immunoreactivity in the three structures and that this release is greater after the avoidance task. The present findings suggest a differential regional involvement of endogenous benzodiazepine-mediated mechanisms in memory modulation, according to the task undertaken