BEHAVIORAL AND DEVELOPMENTAL CHANGES ASSOCIATED WITH PSYCHOACTIVE DRUGS IN HUMANS AND IN A DROSOPHILA MELANOGASTER MODEL
Drosophila Melanogaster; Abuse drugs; Addiction; Crack Cocaine; Marijuana; Nicotine; Cocaine.
Psychoactive substances interact with the brain and cause changes in mood, consciousness, thoughts, feelings, or behavior. Among the most used are marijuana, nicotine, cocaine, crack cocaine and the like. Crack cocaine consumption leads to public health challenges with an increasing number of children intoxicated by crack cocaine during pregnancy. Substance abuse and dependence is an important areas of research for which animal experiments play a critical role. Drosophila melanogaster is a well-studied and highly treatable genetic model organism for understanding the molecular mechanisms of human disease and drug-of-abuse studies. In this context, the main objective of this work was to describe the maternal, fetal and neonatal consequences of crack use during pregnancy and to describe the changes in the development and behavior of D. Melanogaster. Two systematic reviews with meta-analysis were performed. The first, based on observational studies, had the use of the random effects model, odds ratio (OR) for categorical variables, and mean difference for continuous variables. Statistical heterogeneity was assessed using the I-square statistic and the risk of bias was assessed using the Newcastle–Ottawa Quality Rating Scale. Ten studies met the eligibility criteria and were used for data extraction. The second was carried out from pre-clinical studies, including experimental studies with Drosophila melanogaster exposed to psychoactive drugs. Two reviewers independently extracted data. DerSimonian and Laird's random effects model was used, using the inverse variance method to assign the weight of the studies. Statistical heterogeneity was verified by Cochran's Q test and inconsistency by the I² statistic. Sensitivity analysis was performed in case of significant heterogeneity, removal of one study at a time, and subgroup analysis. For all analyses, an alpha value of 5% was adopted, using the metan package of the Stata v13.0 software (StataCorp, College Station, TX, USA). The quality of reports was assessed using the adapted CAMARADES. In the results, it was observed that the use of crack during pregnancy was associated with significantly higher chances of premature birth [(OR), 2.22; 95% confidence interval (CI), 1.59–3.10], placental displacement (OR, 2.03; 95% CI 1.66–2.48), smaller head circumference (−1.65 cm; 95% CI −3.12 to −0.19), small for gestational age (SGA) (OR, 4.00; 95% CI 1.74–9.18) and low birth weight (LBW) (OR , 2.80; 95% CI 2.39–3.27). Forty-nine studies met the eligibility criteria and were used to extract data from the second review, but only fifteen were eligible for meta-analysis. We observed that cocaine exposure causes increased locomotor activity in D. melanogaster (SMD, -1.11; 95% CI -1.81, -0.42). For the other variables, no significant difference was observed due to the great heterogeneity of the studies. This analysis provides clear evidence that crack contributes to adverse perinatal outcomes. Maternal or prenatal crack exposure is linked to low birth weight, preterm birth, placental displacement, and smaller head circumference. Drugs of abuse such as cocaine, nicotine and marijuana cause molecular, morphological, behavioral and survival changes in D. melanogaster at different stages of development.