Postnatal Brain Development and Psychotropic Drugs. Effects on Animals and Animal Models of Depression and Attention-Deficit/Hyperactivity Disorder

Abstract

In recent years an increased use of psychotropic medication in children has been observed, but little is known about the influence of this medication on brain maturation. Probably, because of methodological problems and/or ethical aspects. It means that only naturalistic observational studies might allow to get some insight in humans. But even animal studies touching this issue are scarce and heterogeneous. Nevertheless, postnatal brain development is highly sensitive to the effects of psychotropic drugs, either in the short- and/or long-term. Therefore, more and better information is needed. The main targets of psychotropic drugs are the monoaminergic transmitter systems that are related to brain networks for motor behavior, motivation, emotion, and cognition. In order to elucidate the mechanisms of drug development interactions and their long-term consequences on brain and behavior, animal studies might provide a good basis for a better understanding and guidance of research in humans. Hence, this article reviews the possible influence of those psychotropic drugs on postnatal brain development in animals (mostly rats and rodents) which are widely used to treat common psychiatric disorders in children and adolescents like depression and attention-deficit/ hyperactivity disorder (ADHD). Moreover this review refers to the obvious problems of the available animal studies (including experimental animal models of child psychiatric disorders) which seem to be of limited value in translating experimental knowledge to the complexity of clinical understanding and practice.

Risks of Stimulant Use for Attention Deficit Hyperactivity Disorder on the Developing Brain: Primum non nocere

“…There is a wealth of research regarding the neuropsychiatric effects of stimulants when used in humans [17][18][19][20][21][22] and animals. [23][24][25][26][27] Importantly, the clinical symptoms of ADHD, including hyperactivity, impulsivity, and short attention span, are reported side effects of stimulants treating ADHD at therapeutic doses. 10 Amphetamine and MPH have both been found to induce ADHD-like symptoms, including increased activity and decreased attention, in animals.…”

“…28 In primates, the chronic administration of d-amphetamine has been shown to cause hypervigilance and tracking of and responding to nonapparent stimuli-symptoms similar to those of paranoid schizophrenia in humans. 23,25,29 In these animal studies, symptoms cognate with psychotic symptoms have been reported as side effects of stimulant medications at therapeutic doses. 21,22 Neuronal Imprinting Human research and collateral animal studies, some using standard prescribed doses, raise the question of an association between the increasing prevalence and chronicity of ADHD and the use of stimulants.…”