Persistent behavioral impairment caused by embryonic methylphenidate exposure in zebrafish

Levin, E.D., Sledge, D., Roach, S., Petro, A., Donerly, S., and Linney, E.
Neurotoxicology and teratology   33(6): 668-73 (Journal)
Registered Authors
Donerly, Sue, Linney, Elwood
methylphenidate, neurotoxicity, zebrafish, learning
MeSH Terms
  • Animals
  • Behavior, Animal/drug effects*
  • Biogenic Monoamines/metabolism
  • Brain/drug effects
  • Brain/embryology
  • Brain Chemistry/drug effects
  • Central Nervous System Stimulants/toxicity*
  • Choice Behavior/drug effects
  • Dose-Response Relationship, Drug
  • Embryo, Nonmammalian/drug effects*
  • Learning/drug effects
  • Memory/drug effects
  • Methylphenidate/toxicity*
  • Reflex, Startle/drug effects
  • Spatial Behavior/drug effects
  • Zebrafish/embryology*
  • Zebrafish/growth & development
21741476 Full text @ Neurotoxicol. Teratol.
As more adults take the stimulant medication methylphenidate to treat attention deficit hyperactivity disorder (ADHD) residual type, the risk arises with regard to the potential risks of early developmental exposure if people taking the medication become pregnant. We studied the neurobehavioral effects of methylphenidate in zebrafish. Zebrafish offer cellular reporter systems, continuous visual access and molecular interventions such as morpholinos to help determine critical mechanisms underlying neurobehavioral teratogenicity. Previously, we had seen that persisting neurobehavioral impairment in zebrafish with developmental chlorpyrifos exposure was associated with disturbed dopamine systems. Because methylphenidate is an indirect dopamine agonist, it was thought that it might also cause persistent behavioral impairment after developmental exposure. Zebrafish embryos were exposed to the ADHD stimulant medication methylphenidate 0–5 days post fertilization (12.5–50 mg/l). They were tested for long-term behavioral effects as adults. Methylphenidate exposure (50 mg/l) caused significant increases in dopamine, norepinepherine and serotonin on day 6 but not day 30 after fertilization. In the novel tank diving test of predatory avoidance developmental methylphenidate (50 mg/l) caused a significant reduction in the normal diving response. In the three-chamber spatial learning task early developmental methylphenidate (50 mg/l) caused a significant impairment in choice accuracy. These data show that early developmental exposure of zebrafish to methylphenidate causes a long-term impairment in neurobehavioral plasticity. The identification of these functional deficits in zebrafish enables further studies with this model to determine how molecular and cellular mechanisms are disturbed to arrive at this compromised state.
Genes / Markers
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Engineered Foreign Genes
Errata and Notes