The role of inducible nitric oxide synthase in cocaine-induced locomotor sensitization.
Experimentally naive male Sprague-Dawley rats (weighing 85-110 g) were used to examine the role of inducible nitric oxide synthase (iNOS) in cocaine-induced locomotor sensitization. Repeated administration of cocaine (15 mg/kg, ip) for 7 consecutive days produced locomotor sensitization. Pretreatment with iNOS inhibitors, L-N(6)-(1-iminoethyl) lysine (NIL) or (-)-epigallocatechin gallate (EGCG; 10 mg/kg, ip), 30 min before cocaine (15 mg/kg, ip) administration totally blocked the development of cocaine-induced locomotor sensitization. Dopamine (DA) receptor binding in the nucleus accumbens (NAC) showed a significant decrease in the density of D(2) receptor and the affinity of D(1) receptor after cocaine treatment. Pretreatment with EGCG or NIL abolished the cocaine-induced changes in these parameters. These results suggest that iNOS may participate in the process of development of locomotor sensitization through the modulation of DA receptors in the NAC.
Park
K
K
College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL 32307, USA.
Vora
U
U
Darling
S F
SF
Kolta
M G
MG
Soliman
K F
KF
D000818:Animals; D001143:Arousal / Q000187:drug effects*; D003042:Cocaine / Q000494:pharmacology*; D019970:Cocaine-Related Disorders / Q000503:physiopathology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000502:physiology*; D052247:Nitric Oxide Synthase Type II; D009714:Nucleus Accumbens / Q000187:drug effects / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000502:physiology; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000502:physiology
D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D003042:Cocaine