Inhibition of nitric oxide synthase in the ventral tegmental area attenuates cocaine sensitization in rats.
1. Male Sprague-Dawley rats were pretreated via bilateral infusion of the VTA with the selective neuronal nitric oxide synthase inhibitor, 7-nitroindazole (0, 8, or 40 ng/hemisphere), prior to each of 7 daily systemic cocaine (30 mg/kg, i.p.) or saline (1 ml/kg) treatments. 2. After a 7-day treatment withdrawal period, rats received a final systemic challenge with either cocaine (30 mg/kg, i.p.) or saline (1 ml/kg). 3. Locomotor and stereotypic activity were measured following the first and last treatments. 4. Daily cocaine treatment led to the development of sensitization to its stereotypic effects as revealed upon drug challenge. 5. The development of sensitization of cocaine-induced stereotypy was completely blocked by daily intra-VTA pretreatment with 7-nitroindazole. 6. In addition, attenuation of the locomotor effects of cocaine challenge was also observed in animals that received daily intra-VTA 7-nitroindazole (40 ng/hemisphere) infusions. 7. The results indicate that VTA nitric oxide is necessary for the development of sensitization of cocaine-induced stereotypic behavior, and that its repeated inhibition may produce lasting effects on the locomotor response to the drug.
Byrnes
J J
JJ
Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine and New England Medical Center, Boston, MA, USA. jbyrnes@opal.tufts.edu
Pantke
M M
MM
Onton
J A
JA
Hammer
R P
RP
D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D007191:Indazoles / Q000008:administration & dosage; D007263:Infusions, Parenteral; D008297:Male; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013239:Stereotyped Behavior; D017557:Ventral Tegmental Area / Q000187:drug effects* / Q000502:physiology
D018765:Dopamine Uptake Inhibitors; D004791:Enzyme Inhibitors; D007191:Indazoles; D019001:Nitric Oxide Synthase; D003042:Cocaine; C080122:7-nitroindazole