Inducible nitric oxide synthase is involved in the mechanisms of cocaine enhanced neuronal apoptosis induced by HIV-1 gp120 in the neocortex of rat.
Cocaine, often abused by human immunodeficiency virus (HIV) infected patients, has been suggested to worsen the HIV associated dementia via unknown mechanisms. Here we report that subchronic treatment with a dose of cocaine (30 mg/kg i.p.), unable per se to cause neuronal death, increases the number of apoptotic cells typically observed in the neocortex of rats treated with HIV-1 gp120 (100 ng given i.c.v.). A pre-treatment with MK801 (0.3 mg/kg i.p.), a NMDA receptor antagonist, L-NAME (10 mg/kg i.p.) and 7-nitroindazole (50 mg/kg i.p.), two specific inhibitors of NOS, or with 1400 W (1 mg/kg s.c.), a selective inhibitor of inducible NOS (iNOS), minimized neurotoxicity by combined administration of cocaine and gp120 thus implicating iNOS. This conclusion is supported by the evidence that cocaine increases brain neocortical citrulline, the co-product of NO synthesis.
Bagetta
G
G
IRCCS C. Mondino, Experimental Neurobiology Center Mondino-Tor Vergata-Santa Lucia, Rome, Italy. gbagett@tin.it
Piccirilli
S
S
Del Duca
C
C
Morrone
L A
LA
Rombolà
L
L
Nappi
G
G
De Alba
J
J
Knowles
R G
RG
Corasaniti
M T
MT
D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis; D003042:Cocaine / Q000494:pharmacology*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D015699:HIV Envelope Protein gp120 / Q000633:toxicity*; D008297:Male; D019579:Neocortex / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D019001:Nitric Oxide Synthase / Q000502:physiology*; D052247:Nitric Oxide Synthase Type II; D051381:Rats; D017208:Rats, Wistar
D000779:Anesthetics, Local; D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D015699:HIV Envelope Protein gp120; D016291:Dizocilpine Maleate; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D003042:Cocaine