Effects of Alcohol on the Acquisition and Expression of Fear Potentiated Startle in Mouse Lines Selectively Bred for High and Low Alcohol Preference

Rationale: Anxiety disorders and alcohol-use disorders frequently co-occur in humans perhaps because alcohol relieves anxiety. Studies in humans and rats indicate that alcohol may have greater anxiolytic effects in organisms with increased genetic propensity for high alcohol consumption. Objectives and Methods: The purpose of this study was to investigate the effects of moderate doses of alcohol (0.5, 1.0, 1.5 g/kg) on the acquisition and expression of anxiety-related behavior using a fear-potentiated startle (FPS) procedure. Experiments were conducted in two replicate pairs of mouse lines selectively bred for high- (HAP1 and HAP2) and low- (LAP1 and LAP2) alcohol preference; these lines have previously shown a genetic correlation between alcohol preference and FPS (HAP\u3eLAP; Barrenha and Chester 2007). In a control experiment, the effect of diazepam (4.0 mg/kg) on the expression of FPS was tested in HAP2 and LAP2 mice. Results: The 1.5 g/kg alcohol dose moderately decreased the expression of FPS in both HAP lines but not LAP lines. Alcohol had no effect on the acquisition of FPS in any line. Diazepam reduced FPS to a similar extent in both HAP2 and LAP2 mice. Conclusions: HAP mice may be more sensitive to the anxiolytic effects of alcohol than LAP mice when alcohol is given prior to the expression of FPS. These data collected in two pairs of HAP/LAP mouse lines suggest that the anxiolytic response to alcohol in HAP mice may be genetically correlated with their propensity toward high alcohol preference and robust FPS

O tratamento farmacológico da fobia social Pharmacologic treatment of social phobia

A fobia social é o medo acentuado e persistente de comer, beber, tremer, enrubescer, falar, escrever, enfim, de agir de forma ridícula ou inadequada na presença de outras pessoas. A fobia social apresenta-se em dois tipos básicos: a circunscrita, restrita a apenas um tipo de situação social, e a generalizada, caracterizada pelo temor a todas ou quase todas situações sociais. As características clínicas da fobia social são a ansiedade antecipatória, os sintomas físicos, a esquiva e a baixa auto-estima. Conforme o rigor diagnóstico, estima-se que 5% a 13% da população geral apresentem sintomas fóbicos sociais que resultem em diferentes graus de incapacitação e limitações sociais e ocupacionais. O tratamento médico de escolha é o uso de medicamentos associados à psicoterapia cognitivo-comportamental. Beta-bloqueadores (atenolol, propranolol), antidepressivos inibidores da monoamino oxidase (IMAO) (fenelzine, tanilcipromina), inibidores reversíveis da monoamino oxidase tipo-A (RIMA) (moclobemida, brofaromina), benzodiazepínicos (clonazepam, bromazepam, alprazolam) e antidepressivos inibidores seletivos de serotonina (ISRS) (paroxetina, sertralina, fluoxetina e fluvoxamina) e alguns outros (venlafaxina, nefazodone, gabapentina, clonidina) têm demonstrado eficácia em inúmeros estudos com diferentes metodologias. Os antidepressivos tricíclicos (imipramina, clomipramina), o ácido valproico e a buspirona têm apresentado resultados negativos. A paroxetina é o medicamento mais estudado com metodologia duplo-cega, com melhores resultados e com boa tolerância. Atualmente, os indivíduos que têm sua vida prejudicada pela fobia social podem, com o tratamento eficaz, adquirir uma postura mais segura em situações sociais.<br>Social phobia is a marked and persistent fear of eating, drinking, trembling, blushing, speaking, writing or doing almost everything in front of people due to concerns about embarrassment or being scrutinized by others. There are two specifiers for social phobia: the circumscribed, for those who just fear one situation; and generalized, for those who fear almost all social situations. The clinical features of social phobia are the anticipatory anxiety, the physical symptoms, the avoidance and the low self-esteem. Depending on diagnostic criteria, it is reported a lifetime prevalence ranging from 5% to 13% of the population resulting in different degrees of occupational and social limitations. The ideal treatment should use antidepressant drug and cognitive-behavior therapy. Beta-blocking drugs (atenolol, propranolol), monoamino oxidase inhibitors - MAOI (fenelzine, tanilcipromine), reversible monoamino oxidase-A inhibitors (moclobemide, brofaromine), benzodiazepines (clonazepam, bromazepam, alprazolam) and serotonin selective recaptors inhibitors - SSRI (paroxetine, sertraline, fluoxetine, fluvoxamine) and some other drugs (venlafaxine, nefazodone, gabapentin, clonidine) have been shown efficacy in several studies with different methodology. The tricyclic antidepressants ( imipramine, clomipramine), valproic acid and buspirone have shown negative results. Paroxetine is the most studied substance in double-blind trials with good results and well tolerated. Nowadays the individuals with social phobia can have a efficacious treatment to get an assertive behavior in social situations