Effects of N-acetylcysteine on amphetamine-induced sensitization in mice

Objective: N-acetylcysteine (NAC) is beneficial in psychiatric conditions, including schizophrenia. Patients with schizophrenia exhibit mesolimbic dopamine hyperfunction consequent to an endogenous sensitization process. This sensitization can be modeled in rodents by repeated exposure to psychostimulants, provoking an enduring amplified response at subsequent exposure. The aim of this study was to investigate the effects of NAC on amphetamine sensitization in mice. Methods: D-amphetamine was administered to C57BL/6 mice three times a week for 3 weeks; the dose was increased weekly from 1 to 3 mg/kg. NAC (60 mg/kg) or saline was administered intraperitoneally before saline or amphetamine during the second and third weeks. After a 4-week washout period, latent inhibition (LI) and the locomotor response to amphetamine 2 mg/kg were assessed. Results: Sensitization disrupted LI and amplified the locomotor response; NAC disrupted LI in control mice. In sensitized animals, NAC attenuated the enhanced locomotion but failed to prevent LI disruption. Conclusion: NAC warrants consideration as a candidate for early intervention in ultra-high risk subjects due to its safety profile and the relevance of its mechanism of action. Supplementing this proposition, we report that NAC attenuates sensitization-induced locomotor enhancement in mice. The finding that NAC disrupted LI incites a cautionary note and requires clarification.

A continuidade do uso de anfetaminas por motoristas de caminhão no Estado de São Paulo, Brasil, a despeito da proibição de sua produção, prescrição e uso / Persistent amphetamine consumption by truck drivers in São Paulo State, Brazil, despite the ban on production, prescription, and use / El uso continuado de anfetaminas por parte de los conductores de camión en el estado de São Paulo, Brasil, a pesar de la prohibición de su producción, prescripción y uso

O uso de anfetaminas por motoristas de caminhão com fins ocupacionais é amplamente reconhecido, entretanto, no mês de outubro de 2011, sua produção e uso foram proibidos através de uma resolução da Agência Nacional de Vigilância Sanitária (ANVISA). O objetivo deste estudo foi identificar o uso de anfetaminas entre motoristas de caminhão após a implementação da referida resolução. Uma amostra de conveniência de 427 motoristas de caminhão foi abordada em rodovias do Estado de São Paulo, Brasil, durante o ano de 2012. Os participantes foram solicitados a responder um instrumento de pesquisa estruturado, assim como fornecer uma amostra de urina para avaliar o uso recente de anfetaminas através de análise toxicológica. Entre os motoristas avaliados, 7% fizeram uso recente de alguma substância ilícita, dos quais 2,7% usaram anfetaminas. Aparte a periculosidade associada ao uso de anfetaminas, assim como a despeito da resolução que o regulamenta, esse uso continua entre os motoristas de caminhão. Assim, sugere-se que as autoridades competentes fiscalizem a posse, assim como o uso de anfetaminas no contexto do trânsito.

Amphetamine use by truck drivers for occupational purposes is widely known. The production and consumption of amphetamines was banned by the Brazilian National Health Surveillance Agency (ANVISA) in October 2011. This study analyzes persistent amphetamine use by truck drivers since the ban was implemented. A convenience sample of 427 truck drivers was taken along highways in São Paulo State in 2012. Participants were asked to answer a structured questionnaire and provide a urine sample to screen for recent amphetamine consumption through toxicological analysis. Among the interviewed drivers, 7% had used some illicit drug recently and 2.7% had used amphetamines. Amphetamines are still consumed by truck drivers despite the risks and the recent ban. The authorities should thus monitor the possession and use of amphetamines by drivers in order to effectively enforce the ban.

El uso de anfetaminas con fines profesionales entre los conductores de camiones es ampliamente reconocido, sin embargo, en octubre de 2011, su producción y uso fueron prohibidos por una resolución de la Agencia Nacional de Vigilancia Sanitaria (ANVISA). El objetivo de este estudio fue identificar el uso de anfetaminas entre conductores de camión después de la implementación de esa resolución. Una muestra de conveniencia compuesta por 427 conductores de camiones fue abordada en las carreteras del estado de São Paulo, Brasil, en el año 2012. A los participantes se les pidió rellenar una encuesta estructurada, así como dar una muestra de orina para determinar el consumo reciente de anfetaminas, a través de análisis toxicológico. Entre los conductores evaluados, el 7% consumió recientemente algún estupefaciente, de los cuales un 2,7% había consumido anfetaminas. Aparte de los peligros asociados al uso de anfetaminas, y de la resolución que lo regula, ese uso sigue vigente entre los conductores de camión. Por lo tanto, se sugiere que las autoridades competentes supervisen la posesión, así como el consumo de anfetaminas, en el tráfico rodado.

Central noradrenergic & dopaminergic modulation of brewer's yeast-induced inflammation & nociception in rats.

The possibility of central noradrenergic and dopaminergic modulation of Brewer's yeast-induced peripheral inflammation was investigated in rats. Centrally administered noradrenaline (NA), amphetamine, which liberates NA and dopamine in the central nervous system and L-dopa, the precursor of dopamine significantly suppressed paw oedema. Conversely, the beta-adrenoceptor blocker, propranolol, catecholaminergic neuron degenerator, 6-hydroxydopamine (6-OHDA), dopaminergic antagonist, haloperidol and dopamine synthesis inhibitor, alpha-methyl para tyrosine (AMPT) augmented paw oedema. In addition, 6-OHDA and haloperidol produced significant reduction in pain threshold. The results of this study indicate that central NA and dopamine exert inhibitory effects on Brewer's yeast-induced peripheral inflammation.

Effect of apomorphine on rat motor activity induced by fencamfamine and other indirect psychostimulant drugs

We evaluated the effects of low doses of apomorphine on the stimulant behavioral effects induced by amphetamine (2.5 mg/Kg), fencamfamine (6.0 mg/Kg) and cocaine (15,0 mg/Kg). Rats received 0.02 mg/Kg of apomorphine (sc) and 30 min later were injected with one of the stimulants.Motor activity including locomotion, rearing and sniffing was quantified in the animals home cages for 60 min at 15-min intervals. All stimulant drugs induced hyperactivity. When apomorphine was administered before cocaine, but not when administered before fencmfamine or amphetamine, distinctive changes occurred. The behavioral pattern resulting from high stimulation was replaced by that related to low stimulation, suggesting that apomorphine induces a transfer in the predominant behvior in cocaine-, and partially in fencamfamine-, but not in amphetamine-treated animals, by decreasing the intensity of the stereotyped effect. While no changes occured when apomorphine was administered before amphetamine, the fencamfamine group showed intermediate alterations (nonsignificant changes in sniffing but a significant increase in rearing behavior). These results are discussed in terms of the different mechanisms of presynaptic action of the drugs studied

Diferences between the motor effects induce by apomorphone and by amplhetamine in the male albin rat / Diferencias entre los efectos motores inducidos por la apomorfina y la anfetamina en ratones

Although apomorphine and amphetamine act via dopaminergic receptors, their motor effects have some unexplained differences, which have not been sufficiently studied. In this work either drug induced a quite similar pattern of stereotyped behavior which was antagonized by a low dose of haloperidol in both cases. The slight increase in locomotion seen after apomorphine appeared after stereotypies had completely developed and was also blocked by the same dose of haloperidol. In contrast, the amphetamine-induced locomotor stimulation preceded or acompanied the development of stereotypies and it was potentiated by the low dose of haloperidol. We concluded that apomorphine acts mainly at the striatal level to induce both locomotion and stereotyped behavior, whereas amphetamine acts in the striatum to produce stereotypies and in the accumben to increase locomotion.

Tratamiento farmacologico del transtorno de deficit de la atencion / Pharmacologic treatment of the attention deficit disorder

Se revisa la literatura acerca del tratamiento farmacologico del transtorno del deficit de la atencion. Pocas modificaciones importantes se han realizado durante los ultimos 10 anos. Los estimulantes son efectivos en el aumento de la atencion y en la disminucion de la hiperactividad. Sin embargo persiste controversia acerca de su uso. Aunque algunso postulan efectos positivos sobre el rendimiento academico esto no es tan claro, y ademas no existe evidencia clara sobre la efectividad de los estimulantes en mejorar el pronostico a largo plazo. Se describe el uso clinico de las drogas en el TDA.