ADHD Drugs Could Have Generational Effect

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The parental environment can have a strong influence on the development of their children and subsequent phenotype (their physical traits). There is now growing evidence that these parental effects can be transgenerational – meaning that they’re able to span multiple generations. For example, stressful situations (e.g. early life stress), and exposure to some drugs and pollutants can have transgenerational effects on physiology and behaviour. If these effects are common, they would have important implications for understanding how natural populations respond to changing environments, including anthropogenic effects (which are effects caused by humans, e.g. climate change, exposure to pollutants), and how the experiences of our ancestors can affect our health and susceptibility to disease. However, whether these results can be generalised past the few groups where these effects have been investigated, is not certain. The researchers of the study in question examined the transgenerational effects of a common pharmaceutical drug on natural behaviours of Trinidadian guppies (a freshwater tropical fish). The study’s main aim was to determine whether parent’s exposure to MPH (a drug commonly given for ADHD treatment) leads to transgenerational effects in following generations that were not directly given the drug.

MPH (Methylphenidate hydrochloride), commercially known as Ritalin or Concerta, is a stimulant that was predicted to have transgenerational effects. It’s widely prescribed to individuals with ADHD (attention-deficit/hyperactive disorder), which is a disorder that is characterised by imbalances in 2 main systems of the brain (the dopaminergic system, which uses the neurotransmitter dopamine, and noradrenergic system, which uses the neurotransmitter noradrenaline), and this results in reduced focus and increased impulsivity/over-activity. MPH has similar neurochemical properties to similar drugs like cocaine and, in rodents, repetitive exposure to either MPH or cocaine can lead to an increased occurrence of stereotypical behaviours, drug-seeking, and affective disorders. As mentioned, this study investigated if MPH causes transgenerational effects in Trinidadians guppies. In general, guppies and other fish are increasingly being used for neurological research because of their similarity to mammals in neurodevelopmental patterns, functional brain organisation, and neurocircuitry, including the dopaminergic system.

In the study, from 1 month of age and through adolescence and into adulthood, both first-generation male and female guppies were exposed to a low, steady dose of MPH via the water they lived in, and their behaviour analysed to determine if there were any behavioural effects present in the first-generation and in the 3 subsequent generations that were not administered the drug directly. Because continuous treatment with therapeutic levels of MPH reduced exploration and increased anxiety in rodents, the researchers predicted that guppies continuously treated with MPH would reduce their exploration of a new environment. And as predicted, this is what was observed. There was a significant effect on chronic MPH on the exploratory behaviour of the first-generation males, but not females, and so the study focussed on the transgenerational paternal effects of MPH exposure. The control guppies were also treated in the same manner, however they were only administered the vehicle which carried the drug, so were not given the active drug.

To investigate the transgenerational effects of MPH treatment, first-generation fish were mated using a specific design to produce 4 offspring (the second-generation) treatment groups, which were maintained to produce the third and fourth generations. The second to fourth generations were not given MPH or vehicle. From the results, the offspring (second generation) and great-grandoffspring (fourth generation) of MPH treated males showed altered behaviour relative to controls, demonstrating that MPH can cause transgenerational effects through the paternal line. Although the second and fourth generations showed significant MPH effects, this was not the case for the first-generation female and third-generation guppies; the published discussion of the study offers possible explanations for the lack of significant effect of MPH on these guppies. Furthermore, MPH treatment did not have a significant effect on whole brain dopamine levels, which suggests that the behavioural differences in the offspring were not directly controlled by changes in dopamine levels in the brain. And as mentioned earlier, fish and mammals share functional similarities in their brain neurochemistry and behaviour, and because of this the researchers suggest that their results may be relevant for mammals, including male adolescents and adults who are prescribed MPH.

Original Link: https://www.nature.com/articles/s41598-021-83448-x

Original Paper: De Serrano, A.R., Hughes, K.A and Rodd, F.H. (2021) “Paternal exposure to a common pharmaceutical (Ritalin) has transgenerational effects on the behaviour of Trinidadian guppies.” Scientific Reports. DOI: https://doi.org/10.1038/s41598-021-83448-x

Featured Image: Photo by Juan Pablo Serrano Arenas from Pexels

Edited by Cyrus Rohani-Shukla

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