RESUMO
Opioid abuse continues to plague society, and in recent years, there has been an epidemic, leading to increased addiction and death. It is poorly understood how prenatal opioid use affects the lives of children. The aim of this work was to evaluate the effect of early embryonic codeine or morphine exposure in zebrafish (Danio rerio), examining gastrulation progression (epiboly), teratogenic effects, mortality and locomotor behavior response to light/dark cycles. Zebrafish embryos were exposed to codeine or morphine (designated C or M) at 1, 5 or 10 mg/L (designated 01, 05 or 10, respectively) from 3 to 24 h postfertilization (hpf) or from 3 to 48 hpf (designated -24 or - 48 for 1 or 2 days of exposure, respectively). The C10-24, C01-48, C05-48 and C10-48 groups showed significantly smaller eyes than control larvae at 7 days postfertilization (dpf). Locomotor behavior of control larvae in light/dark cycles showed greater swimming time and distance in dark cycles. Two-day codeine exposure produced strong effects, showing no significant response due to light/dark cycles in distance moved. Morphine exposed groups showed similar effects as observed in 2-day codeine exposed groups, showing less large movement activity and also no significant difference between inactive duration in response to light/dark cycles. In conclusion, we observed low teratogenic effects and mortality effects. Animals exposed to high levels and higher exposure times of opioids were hypoactive, relative to controls, in the dark period. Future studies will be needed to understand the neural defects producing behavior changes.
Assuntos
Analgésicos Opioides/toxicidade , Atividade Motora/efeitos dos fármacos , Animais , Codeína/toxicidade , Larva/efeitos dos fármacos , Larva/crescimento & desenvolvimento , Morfina/toxicidade , Natação , Peixe-Zebra/embriologiaRESUMO
The mean population age of the United States continues to increase, and data suggest that by the year 2060 the population of people over the age of 65 will more than double, providing a potentially massive strain on health care systems. Research demonstrates individuals 65 and older continue to consume ethanol, often at high levels. However, preclinical animal models are still being developed to understand how ethanol might interact with the aged population. The current experiments investigated differential body temperature responses in aged rats compared to adult rats and adolescent rats. Aged (19 months of age), adult (70 days of age), or adolescent (30 days of age) male Sprague Dawley rats were administered 1.0 g/kg, 2.0 g/kg, or 3.0 g/kg ethanol, intraperitoneally (i.p.), in a balanced Latin square design. Prior to ethanol administration, a core body temperature via an anal probe was obtained, and then repeatedly determined every 60 min following ethanol exposure for a total of 360 min. In addition, a blood sample was obtained from a tail nick 60, 180, and 300 min following the ethanol injection to investigate the relationship of ethanol levels and body temperature in the same animals. Aged rats had significantly greater reductions in body temperature compared to either adult or adolescent rats following both the 2.0 g/kg and 3.0 g/kg ethanol injection. Additionally, adolescent rats cleared ethanol significantly faster than aged or adult animals. These experiments suggest body temperature regulation in aged rats might be more sensitive to acute ethanol compared to adult rats or adolescent rats. Future studies are needed to identify the neurobiological effects underlying the differential sensitivity in aged rats to ethanol.
Assuntos
Consumo de Bebidas Alcoólicas/efeitos adversos , Regulação da Temperatura Corporal/efeitos dos fármacos , Etanol/toxicidade , Hipotermia/induzido quimicamente , Fatores Etários , Consumo de Bebidas Alcoólicas/sangue , Consumo de Bebidas Alcoólicas/fisiopatologia , Animais , Concentração Alcoólica no Sangue , Etanol/sangue , Hipotermia/sangue , Hipotermia/fisiopatologia , Masculino , Ratos Sprague-Dawley , Medição de Risco , Fatores de Risco , Fatores Sexuais , Fatores de TempoRESUMO
The average age of the population in the United States and other countries is increasing. Understanding the health consequences in the aged population is critical. Elderly individuals consume ethanol, often at elevated rates, and in some cases in a binge episode. The present study sought to investigate whether binge-like ethanol exposure in aged male rats produced differential health and behavioral effects compared to adult male and adolescent male rats. Subjects were exposed to either 1.0 g/kg or 2.0 g/kg ethanol every other day via intraperitoneal injection for 20 days, and tested on a variety of behavioral measures and body weight. Binge-like ethanol exposure produced differential effects on body weight between aged and adolescent and adult rats. In addition, aged rats had a significantly longer loss of righting reflex and demonstrated a trend toward tolerance following the 2.0-g/kg exposure. No significant effects on anxiety-like behavior as measured by open arm entries, depressive-like symptoms as measured by immobility in the forced swim test, or cognitive performance as measured by latency and path length in the Morris water maze were found. These results demonstrate that aged animals are differentially sensitive to the impact of chronic intermittent ethanol exposure in some, but not all behaviors. Future research is needed to understand the mechanisms of these differential effects.