Involvement of NO/cGMP pathway in toluene-induced locomotor hyperactivity in female rats.
BACKGROUND
Nitric oxide (NO) is implicated in the acute locomotor activating effects of some addictive drugs such as amphetamine, caffeine, and PCP, but has not been investigated in the case of toluene.


OBJECTIVE
This study determined the contribution of the NO-cyclic GMP (cGMP) pathway to locomotor stimulant effects of toluene.


METHODS
Locomotor activity was measured for 90 min immediately following toluene (500-1,000 mg/kg, IP) or corn oil treatments in Sprague-Dawley female rats. A NO generator, sodium nitroprusside (SNP) (3 and 6 mg/kg), a NO precursor, L-arginine ( L-Arg) (250 mg/kg), a NO synthase inhibitor, N(G)-nitro- L-arginine methyl ester (L-NAME) (5-20 mg/kg, IP), and a soluble guanylyl cyclase inhibitor, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) (10 mg/kg) were injected 5 min before toluene (750 mg/kg, IP) treatment. The combination effects of SNP with L-NAME, L-arginine with L-NAME, SNP with ODQ and L-arginine with ODQ on toluene-induced locomotor hyperactivity were also determined. RESULTS. The locomotor hyperactivity induced by toluene was significantly inhibited by SNP and L-arginine, but enhanced by L-NAME and ODQ. SNP and L-arginine completely reversed the combined effects of L-NAME and toluene to a basal level and abolished the enhancing effects of ODQ.


CONCLUSIONS
The results suggested that NO/cGMP-dependent mechanism might be involved in toluene-induced locomotor activity in rats.
Chan
Ming-Huan
MH
Institute of Pharmacology and Toxicology, Tzu Chi University, 701, Section 3, Chung-Yang Road, Hualien, Taiwan, ROC.
Chien
Te-Hsiung
TH
Lee
Pei-Yu
PY
Chen
Hwei-Hsien
HH
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D006152:Cyclic GMP / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D006948:Hyperkinesis / Q000139:chemically induced* / Q000523:psychology; D007274:Injections, Intraperitoneal; D009043:Motor Activity / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052248:Nitric Oxide Synthase Type I; D009599:Nitroprusside / Q000494:pharmacology; D010069:Oxadiazoles / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D014050:Toluene / Q000494:pharmacology*
C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D004791:Enzyme Inhibitors; D009419:Nerve Tissue Proteins; D020030:Nitric Oxide Donors; D010069:Oxadiazoles; D011810:Quinoxalines; D009599:Nitroprusside; D009569:Nitric Oxide; D014050:Toluene; D001120:Arginine; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; D006162:Guanylate Cyclase; D006152:Cyclic GMP; D019331:NG-Nitroarginine Methyl Ester