Acute neurobehavioral effects of toluene: involvement of dopamine and NMDA receptors.
Toluene, a widely used and commonly abused organic solvent, causes a variety of behavioral disturbances in both humans and animals. In this study, the effects of toluene on locomotor activity, motor coordination, and passive avoidance learning, along with the possible mechanism underlying these toluene-induced behavioral manifestations, were investigated. Sprague-Dawley rats were tested in the open field test, rotarod test, and step-through avoidance learning task after receiving toluene (250-750 mg/kg, i.p.). Toluene dose-dependently produced locomotor hyperactivity, motor incoordination, and memory impairment. In order to determine the possible roles of dopamine and NMDA receptors in these behavioral responses to toluene, dopamine D1 receptor antagonist SCH23390, D2 receptor antagonist raclopride, D3 receptor antagonist nafadotride, or d-serine, a co-agonist at the glycine binding site of NMDA receptors, were given prior to toluene administration. SCH23390, raclopride, and nafadotride attenuated locomotor hyperactivity, but not motor incoordination and memory impairment in response to toluene, whereas d-serine reduced all the toluene-induced behavioral alterations. These findings suggest that blockade of NMDA receptors may play a critical role in acute toluene-induced locomotor hyperactivity, motor incoordination, and memory impairment, and that dopamine neurotransmission may be specifically involved in locomotor hyperactivity.
Lo
Pi-Shih
PS
Institute of Pharmacology and Toxicology, Tzu Chi University, Hualien, Taiwan.
Wu
Chia-Yen
CY
Sue
Hong-Zher
HZ
Chen
Hwei-Hsien
HH
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects*; D001552:Benzazepines / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009281:Naphthalenes / Q000494:pharmacology; D004856:Postural Balance / Q000187:drug effects; D011759:Pyrrolidines / Q000494:pharmacology; D020891:Raclopride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000187:drug effects / Q000502:physiology*; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors; D050637:Receptors, Dopamine D3 / Q000037:antagonists & inhibitors / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology*; D012694:Serine / Q000494:pharmacology; D014050:Toluene / Q000633:toxicity*
D001552:Benzazepines; D018492:Dopamine Antagonists; D009281:Naphthalenes; D011759:Pyrrolidines; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D050637:Receptors, Dopamine D3; D016194:Receptors, N-Methyl-D-Aspartate; C534628:SCH 23390; D014050:Toluene; D020891:Raclopride; D012694:Serine; C097285:nafadotride