title: Sources of variation in the design of preclinical studies assessing the effects of amphetamine-type stimulants in pregnancy and lactation.
abstract: The prevalence of drug use during pregnancy has increased in recent years and the amount of drug-exposed babies has therefore increased. In order to assess the risk associated with this there has been an increase in the amount of preclinical studies investigating the effects of prenatal and postnatal drug exposure on the offspring. There are many challenges associated with investigating the developmental and behavioural effects of drugs of abuse in animal models and ensuring that such models are appropriate and clinically relevant. The purpose of this review is to illustrate the variation in the design of preclinical studies investigating the effects of the amphetamine-type stimulants taken during pregnancy and/or lactation in animal models. Methamphetamine, methylendioxymethamphetamine and amphetamine were included in this review. The protocols used for exploring the effects of these drugs when taking during pregnancy and/or lactation were investigated and summarised into maternal experimental variables and offspring experimental variables. Maternal experimental variables include animals used, mating procedures and drug treatment and offspring experimental variables include litter standardisation, cross fostering, weaning and behaviours and parameters assessed. The findings in this paper suggest that there is a large diversity and little consistency among these studies and so the interpretation of these results may not be as clinically relevant as previously thought. For this reason, the importance of steering the preclinical studies in a direction that is most clinically relevant will be an important future recommendation. This will also allow us to be more confident in the results obtained and confident that the human situation is being replicated as closely as possible.
authors.affiliation: Discipline of Pharmacology and Therapeutics, School of Medicine, National University of Ireland, Galway, Ireland; Galway Neuroscience Centre, National University of Ireland, Galway, Ireland. Electronic address: k.mcdonnelldowling1@nuigalway.ie.
authors.forename: Kate
authors.initials: K
authors.lastname: McDonnell-Dowling
authors.affiliation: Discipline of Pharmacology and Therapeutics, School of Medicine, National University of Ireland, Galway, Ireland; Galway Neuroscience Centre, National University of Ireland, Galway, Ireland.
authors.forename: John P
authors.initials: JP
authors.lastname: Kelly
mesh_terms: D000661:Amphetamine / Q000008:administration & dosage / Q000633:toxicity; D000662:Amphetamines / Q000008:administration & dosage* / Q000633:toxicity*; D000818:Animals; D000831:Animals, Newborn; D000697:Central Nervous System Stimulants / Q000008:administration & dosage* / Q000633:toxicity*; D004195:Disease Models, Animal; D005260:Female; D007774:Lactation; D008694:Methamphetamine / Q000008:administration & dosage / Q000633:toxicity; D051379:Mice; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000008:administration & dosage / Q000633:toxicity; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D012107:Research Design
chemical_list: D000662:Amphetamines; D000697:Central Nervous System Stimulants; D008694:Methamphetamine; D000661:Amphetamine; D018817:N-Methyl-3,4-methylenedioxyamphetamine
keywords: Amphetamine; Animal model; Methamphetamine; Methylendioxymethamphetamine; Neurodevelopment; Pregnancy