Paternal exposure to a common pharmaceutical (Ritalin) has transgenerational effects on the behaviour of Trinidadian guppies.

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.

Experimentally altered male mating behaviour affects offspring exploratory behaviour via nongenetic paternal effects.

Evidence is emerging that fathers can have nongenetic effects on the phenotypes of their offspring. Most studies have focused on the role that nongenetic modifications to sperm can have on offspring phenotype; however, fathers can also have nongenetic effects on offspring through their interactions with females, called female-mediated paternal effects. These effects can occur in situations where male phenotype, e.g. behaviour or morphology, affects female stress and/or provisioning of offspring. These effects are potentially widespread, but few studies have explicitly investigated the role of female-mediated paternal effects on offspring phenotype. Here, we asked if male mating interactions can affect offspring via female mediated paternal effects in the Trinidadian guppy, Poecilia reticulata. To do this, we manipulated mating behaviour by: (i) administering a drug known to affect the neurotransmitter dopamine, and (ii) varying the familiarity of potential mates, which affects attractiveness in this species. With these treatments, we successfully manipulated the mating behaviour of male guppies and female preference for those males. Further, we found significant effects of sire mating behaviour, sire drug treatment, and parental familiarity status on behavioural measures of offspring anxiety in response to a novel object. Because Control offspring of 'familiar' and 'unfamiliar' pairs differed in their behaviour, our results cannot be solely attributed to potential nongenetic modifications to sperm caused by the drug. These results emphasize the importance of female-mediated paternal effects, including those caused by altered male mating behaviour, in shaping offspring phenotype.

Effects of methylphenidate on responses to novelty in a teleost fish (Poecilia reticulata).

Novelty seeking, the willingness to explore novel stimuli, can have important fitness consequences. The neurotransmitter dopamine has been linked to this behavior in studies on lab animals including rodents and fish; however, few studies have investigated this association in individuals from natural populations. Trinidadian guppies (Poecilia reticulata) show variation in willingness to explore novel objects and environments, and females tend to show a preference for novel males. In this study, we asked whether we could enhance interest in several types of novel stimuli in lab-reared, female Trinidadian guppies by administering methylphenidate hydrochloride, a stimulant known to increase dopamine levels. We scored their responses to three different types of novelty: novel environments, objects, and males. Treated females showed enhanced exploratory behavior: they traversed relatively more inner squares of the novel environment (open-field test); they spent more time inspecting a novel object; and they showed greater interest in the second male guppy to which they were exposed than control fish. We also found a positive association between our metrics of exploration in the open field and novel object tests. Our other assays suggest that these differences were not the result of increased activity or reduced levels of stress. Therefore, our results suggest that dopamine plays a role in the responsiveness of guppies to novelty; this opens the door to studies of behavioral mechanisms in natural populations.

Casting a wider fish net on animal models in neuropsychiatric research.

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.