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


OBJECTIVE
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.


CONCLUSIONS
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.
Chien
Te-Hsiung
TH
Institute of Pharmacology and Toxicology, Tzu Chi University, 701, Section 3, Chung-Yang Road, Hualien, 970, and Cheng Hsin Rehabilitation Medical Center, Taipei, Taiwan.
Chan
Ming-Huan
MH
Tang
Yu-Chi
YC
Chen
Hwei-Hsien
HH
D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000254:growth & development; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005260:Female; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D011247:Pregnancy; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D012018:Reflex / Q000187:drug effects; D013997:Time Factors; D014050:Toluene / Q000097:blood / Q000633:toxicity*
D018691:Excitatory Amino Acid Antagonists; D014050:Toluene; D007649:Ketamine; D016291:Dizocilpine Maleate