Neuropsychiatric disorders, such as schizophrenia, are associated with abnormal brain development. In this review, we discuss how studying dimensional components of these disorders, or endophenotypes, in a wider range of animal models will deepen our understanding of how interactions between biological and environmental factors alter the trajectory of neurodevelopment leading to aberrant behavior. In particular, we discuss some of the advantages of incorporating studies of brain and behavior using a range of teleost fish species into current neuropsychiatric research. From the perspective of comparative neurobiology, teleosts share a fundamental pattern of neurodevelopment and functional brain organization with other vertebrates, including humans. These shared features provide a basis for experimentally probing the mechanisms of disease-associated brain abnormalities. Moreover, incorporating information about how behaviors have been shaped by evolution will allow us to better understand the relevance of behavioral variation to determine their physiological underpinnings. We believe that exploiting the conservation in brain development across vertebrate species, and the rich diversity of fish behavior in lab and natural populations will lead to significant new insights and a holistic understanding of the neurobiological systems implicated in neuropsychiatric disorders.

Evidence is emerging that paternal effects, the nongenetic influence of fathers on their offspring, can be transgenerational, spanning several generations. Methylphenidate hydrochloride (MPH; e.g. Ritalin) is a dopaminergic drug that is highly prescribed to adolescent males for the treatment of Attention-deficit/hyperactivity disorder. It has been suggested that MPH could cause transgenerational effects because MPH can affect the male germline in rodents and because paternal effects have been observed in individuals taking similar drugs (e.g. cocaine). Despite these concerns, the transgenerational effects of paternal MPH exposure are unknown. Therefore, we exposed male and female Trinidadian guppies (Poecilia reticulata) to a low, chronic dose of MPH and observed that MPH affected the anxiety/exploratory behaviour of males, but not females. Because of this male-specific effect, we investigated the transgenerational effects of MPH through the paternal line. We observed behavioural effects of paternal MPH exposure on offspring and great-grandoffspring that were not directly administered the drug, making this the first study to demonstrate that paternal MPH exposure can affect descendants. These effects were not due to differential mortality or fecundity between control and MPH lines. These results highlight the transgenerational potential of MPH.

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