A comparative study on the effects of the benzodiazepine midazolam and the dopamine agents, apomorphine and sulpiride, on rat behavior in the two-way avoidance test

In recent years. studies in behavioral pharmacology have shown the involvement of dopaminergic mechanisms in avoidance behavior as assessed by the two-way active avoidance test (CAR). Changes in dopaminergic transmission also occur in response to particularly threatening challenges. However, studies on the effects of benzodiazepine (BZD) drugs ill this test are still unclear. Given the interplay of dopamine and other neurotransmitters in the neurobiology of anxiety and schizophrenia the aim of this work was to evaluate the effects of systemic administration of midazolam, the dopaminergic agonist apomorphine, and the D(2) receptor antagonist sulpiride using the CAR, a test that shows good sensitivity to typical neuroleptic drugs. Whereas midazolam did not alter the avoidance response. apomorphine increased and sulpiride reduced them in this test. Escape was not affected by any drug treatments. Heightened avoidance was not associated with the increased motor activity caused by apomorphine. In contrast with the benzodiazepine midazolam, activation of post-synaptic D(2) receptors with apomorphine facilitates, whereas the D(2) receptor antagonism with sulpiride inhibited the acquisition of the avoidance behavior. Together, these results bring additional evidence for a role of D(2) mechanisms in the acquisition of the active avoidance. (C) 2009 Elsevier Inc. All rights reserved.

Clinical risk factors for osteoporotic fractures in Brazilian women and men: the Brazilian Osteoporosis Study (BRAZOS)

The Brazilian Osteoporosis Study (BRAZOS) is the first epidemiological study carried out in a representative sample of Brazilian men and women aged 40 years or older. The prevalence of fragility fractures is about 15.1% in the women and 12.8% in the men. Moreover, advanced age, sedentarism, family history of hip fracture, current smoking, recurrent falls, diabetes mellitus and poor quality of life are the main clinical risk factors associated with fragility fractures. The Brazilian Osteoporosis Study (BRAZOS) is the first epidemiological study carried out in a representative sample of Brazilian men and women aged 40 years or older with the purpose of identifying the prevalence and the main clinical risk factors (CRF) associated with osteoporotic fracture in our population. A total of 2,420 individuals (women, 70%) from 150 different cities in the five geographic regions in Brazil, and all different socio-economical classes were selected to participate in the present survey. Anthropometrical data as well as life habits, fracture history, food intake, physical activity, falls and quality of life were determined by individual quantitative interviews. The representative sampling was based on Brazilian National data provided by the 2000 and 2003 census. Low trauma fracture was defined as that resulting of a fall from standing height or less in individuals 50 years or older at specific skeletal sites: forearm, femur, ribs, vertebra and humerus. Sampling error was 2.2% with 95% confidence intervals. Logistic regression analysis models were designed having the fragility fracture as the dependent variable and all other parameters as the independent variable. Significance level was set as p < 0.05. The average of age, height and weight for men and women were 58.4 +/- 12.8 and 60.1 +/- 13.7 years, 1.67 +/- 0.08 and 1.56 +/- 0.07 m and 73.3 +/- 14.7 and 64.7 +/- 13.7 kg, respectively. About 15.1% of the women and 12.8% of the men reported fragility fractures. In the women, the main CRF associated with fractures were advanced age (OR = 1.6; 95% CI 1.06-2.4), family history of hip fracture (OR = 1.7; 95% CI 1.1-2.8), early menopause (OR = 1.7; 95% CI 1.02-2.9), sedentary lifestyle (OR = 1.6; 95% CI 1.02-2.7), poor quality of life (OR = 1.9; 95% CI 1.2-2.9), higher intake of phosphorus (OR = 1.9; 95% CI 1.2-2.9), diabetes mellitus (OR = 2.8; 95% CI 1.01-8.2), use of benzodiazepine drugs (OR = 2.0; 95% CI 1.1-3.6) and recurrent falls (OR = 2.4; 95% CI 1.2-5.0). In the men, the main CRF were poor quality of life (OR = 3.2; 95% CI 1.7-6.1), current smoking (OR = 3.5; 95% CI 1.28-9.77), diabetes mellitus (OR = 4.2; 95% CI 1.27-13.7) and sedentary lifestyle (OR = 6.3; 95% CI 1.1-36.1). Our findings suggest that CRF may contribute as an important tool to identify men and women with higher risk of osteoporotic fractures and that interventions aiming at specific risk factors (quit smoking, regular physical activity, prevention of falls) may help to manage patients to reduce their risk of fracture.