Toluene exposure during the brain growth spurt reduces behavioral responses to noncompetitive N-methyl-D-aspartate receptor antagonists in adult

Rationale: Toluene exposure during brain growth spurt has been shown to elevate the seizure susceptibility induced by N-methyl-D-aspartate (NMDA). In the present study, behavioral responses to NMDA antagonists were studied to determine whether neonatal toluene exposure produces residual deficits in the NMDA glutamatergic system controlling behaviors. We also investigated if the effect of toluene exposure depends strongly on the developmental stage. Objectives: The long-term effects of neonatal and adolescent toluene exposure on MK-801 and/or ketamine-induced hyperlocomotor activity, motor coordination, hypnotic response, and cognitive deficits in early adulthood were compared. Methods: Sprague-Dawley male rats were treated with toluene (500 mg/kg i.p.) daily over postnatal day (PN) 4-9 or 25-30. Locomotor activity was analyzed in a computerized open-field system, motor coordination was measured by rotarod, hypnotic response was tested by loss of righting reflex, and long-term memory was assessed with the inhibitory avoidance learning task during PN 56-60. Results: Toluene exposure during brain growth spurt reduced behavioral responses including locomotor activity, motor incoordination, and hypnosis to MK-801 and/or ketamine, while leaving cognitive deficits in inhibitory avoidance learning tasks unaffected. No significant change in behavioral responses to NMDA antagonists was observed following adolescent toluene exposure. Conclusion: These results indicate that neonatal but not adolescent toluene exposure produces long-term effects on selective behaviors induced by NMDA antagonists. Theses findings further support the hypothesis that functional changes in NMDA receptors may be related to the neurobehavioral dysfunction associated with fetal solvent syndrome.