Stress-Induced Reinstatement of Drug Seeking: 20 Years of Progress

In human addicts, drug relapse and craving are often provoked by stress. Since 1995, this clinical scenario has been studied using a rat model of stress-induced reinstatement of drug seeking. Here, we first discuss the generality of stress-induced reinstatement to different drugs of abuse, different stressors, and different behavioral procedures. We also discuss neuropharmacological mechanisms, and brain areas and circuits controlling stress-induced reinstatement of drug seeking. We conclude by discussing results from translational human laboratory studies and clinical trials that were inspired by results from rat studies on stress-induced reinstatement. Our main conclusions are (1) The phenomenon of stress-induced reinstatement, first shown with an intermittent footshock stressor in rats trained to self-administer heroin, generalizes to other abused drugs, including cocaine, methamphetamine, nicotine, and alcohol, and is also observed in the conditioned place preference model in rats and mice. This phenomenon, however, is stressor specific and not all stressors induce reinstatement of drug seeking. (2) Neuropharmacological studies indicate the involvement of corticotropin-releasing factor (CRF), noradrenaline, dopamine, glutamate, kappa/dynorphin, and several other peptide and neurotransmitter systems in stress-induced reinstatement. Neuropharmacology and circuitry studies indicate the involvement of CRF and noradrenaline transmission in bed nucleus of stria terminalis and central amygdala, and dopamine, CRF, kappa/dynorphin, and glutamate transmission in other components of the mesocorticolimbic dopamine system (ventral tegmental area, medial prefrontal cortex, orbitofrontal cortex, and nucleus accumbens). (3) Translational human laboratory studies and a recent clinical trial study show the efficacy of alpha-2 adrenoceptor agonists in decreasing stress-induced drug craving and stress-induced initial heroin lapse

Audiometria de alta freqüência: estudo com indivíduos audiologicamente normais High-frequency audiometry: study with normal audiological subjects

Pesquisas recentes apontam a Audiometria Tonal de Alta Freqüência (AT-AF) como um instrumento para o diagnóstico precoce de danos auditivos decorrentes de alguns agentes etiológicos principais, como envelhecimento e exposição a drogas ototóxicas e a intensidades elevadas de ruído. OBJETIVO: Apesar de já existirem várias técnicas desenvolvidas para essa avaliação, algumas não se aplicam à rotina clínica, em função da falta de praticidade e, por vezes, falta de consistência nos resultados. Segundo a literatura, ainda estão por emergir uma metodologia adequada a tal avaliação e valores indicados como referência à normalidade. Forma de Estudo: Clínico prospectivo. MATERIAL E MÉTODO: A presente pesquisa observou o comportamento dos limiares auditivos de alta freqüência em indivíduos jovens e audiologicamente normais e analisou variabilidades acústicas, inter e intra-indivíduos, que de acordo com a literatura, podem interferir na estabilidade dos resultados. CONCLUSÃO: Com os dados obtidos, pôde-se estabelecer valores de média, desvio padrão e mediana, além de valores mínimos e máximos para cada freqüência. Os testes estatísticos não identificaram diferenças significantes na maioria das análises realizadas (entre sexo, interaurais, variabilidades acústicas e intra-indivíduos, no mesmo dia de testes). A variabilidade dos resultados entre os exames de um mesmo indivíduo, realizados em dias deferentes de testes, mostrou ser significante, sendo as médias dos limiares no segundo dia sempre melhores que as do primeiro dia.<br>Recent research studies pointed to High-Frequency Audiometry (HFA) as a tool for early diagnosis of hearing impairment caused by the main etiological agents, such as aging, exposure to ototoxic drugs, and occupational noise. AIM: Although there are already several techniques developed for this assessment, some of them should not be applied to clinical routine, because of their lack of practicability and, sometimes, lack of reliable results. According to the literature, a suitable methodology for such assessment, as well as values indicated as normal reference, are still needed. STUDY DESIGN: Clinical prospective. MATERIAL AND METHOD: The present research study observed auditory thresholds in young and audiologically normal individual with HFA and assessed some variables that could have an influence upon the results. CONCLUSION: Based on the collected data, we were able to established values for mean, standard deviation and median, besides minimum and maximum values for each frequency, for the entire population. Statistical analyses did not identify significant differences between gender and the ears. Moreover, questions related to inter-and intra-individual variability are discussed

Limiares de audibilidade em altas freqüências em crianças com história de otite média secretora bilateral Audibility threshold for high frequencies inchildren with medical history of multiples episodes of bilateral secretory otitis media

Existem achados na literatura de limiares elevados em altas freqüências em crianças com história de otite média secretora. OBJETIVO: Caracterizar os limiares de audibilidade nas altas freqüências em crianças normo-ouvintes com história de múltiplos episódios de otite média secretora bilateral. MATERIAL E MÉTODO: Constituiu-se uma amostra de 31 crianças de ambos os sexos, sendo 14 com até 3 episódios de otite média secretora bilateral (Grupo 1) e 17 com quatro ou mais episódios (Grupo 2). Foi realizada a audiometria tonal por via aérea para as freqüências de 9.000 a 18.000Hz. FORMA DE ESTUDO: Transversal prospectivo. RESULTADOS: Não houve diferença entre os limiares de audibilidade das orelhas direitas e esquerdas dos indivíduos de ambos os grupos para todas as freqüências, porém, houve entre os limiares de audibilidade das orelhas direitas e esquerdas do Grupo 2 em relação ao Grupo 1 para todas as freqüências avaliadas. CONCLUSÕES: 1- Houve uma elevação dos limiares de audibilidade com o aumento das freqüências apresentadas. 2- A audiometria de altas freqüências mostrou-se capaz de separar, em grupos, indivíduos com história de otite média secretora denotando que quatro episódios de otite média já são suficientes para determinar diferenças estatisticamente significantes nos limiares de audibilidade das altas freqüências.<br>Relatively poorer audibility threshold for high frequency was found in children with medical history of multiples episodes of secretory otitis media. AIM: to characterize the audibility threshold for high frequencies in normal-hearing children with medical history of multiples episodes of bilateral secretory otitis media. MATERIALS AND METHODS: a sample of 31 children, from both genders, was divided in two groups: 14 subjects who had not more than 3 episodes of bilateral secretory otitis media (Group 1) and 17 subjects that experienced at least 4 episodes of this condition (Group 2). Pure-tone air conduction audiometry was tested at frequencies 9,000 to 18,000 Hz. STUDY DESIGN: transversal prospective. RESULTS: there was no difference between audibility thresholds comparing right and left ears of subjects of both Group 1 and Group 2 in all tested frequencies. However, there was difference between audibility thresholds between subjects of Group 2 compared to Group 1 in all tested frequencies. CONCLUSION: 1- There was an increase in audibility thresholds with the increase in frequency . 2- High frequency audiometry separates subjects with history of at least four episodes of secretory otitis media, suggesting that these episodes are sufficient to promote statistically significant difference in high frequency thresholds