Persistent effects of subchronic toluene exposure on spatial learning and memory, dopamine-mediated locomotor activity and dopamine D2 agonist binding in the rat.
The effects of subchronic inhalation exposure to toluene (80 ppm, for 4 weeks, 5 days/week, 6 h/day) was studied on spatial learning (postexposure days 3-6) and memory (postexposure day 14) using a water maze, on spontaneous and apomorphine-induced (1 mg/kg, subcutaneously (s.c.)) locomotor activity (postexposure day 17) and on the binding parameters of the dopamine D2 agonist S(-)[N-propyl-3H(N)]propylnorapomorphine ([H]NPA) in membrane preparations of the neostriatum of the rat. Toluene treatment was found to cause a statistically significant impairment in acquisition and retention of the spatial learning task. Furthermore, toluene significantly increased (2-fold) apomorphine-induced locomotion and caused a trend for a 50-60% increase in motility without any significant effect on rearing. Spontaneous locomotion, motility and rearing were not affected by toluene. Toluene treatment produced a significant 30-40% increase in the Bmax values of [3H]NPA and a trend for a 20-30% increase in the KD values. These results indicate that subchronic exposure to toluene in low concentrations causes a slight but persistent deficit in spatial learning and memory, a persistent increase in dopamine-mediated locomotor activity and an increase in the number of dopamine D2 receptors in the rat.
von Euler
G
G
Department of Histology and Neurobiology, Karolinska Institutet, Stockholm, Sweden.
Ogren
S O
SO
Li
X M
XM
Fuxe
K
K
Gustafsson
J A
JA
D000280:Administration, Inhalation; D000818:Animals; D001058:Apomorphine / Q000031:analogs & derivatives* / Q000378:metabolism; D001522:Behavior, Animal / Q000187:drug effects; D015259:Dopamine Agents / Q000378:metabolism*; D007858:Learning / Q000187:drug effects; D008297:Male; D008568:Memory / Q000187:drug effects*; D009043:Motor Activity / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000378:metabolism; D014050:Toluene / Q000633:toxicity*
D015259:Dopamine Agents; D011954:Receptors, Dopamine; D014050:Toluene; C009074:N-n-propylnorapomorphine; D001058:Apomorphine