Evidence for the role of nitric oxide in nicotine-induced locomotor sensitization in mice
- 96 Downloads
Nitric oxide (NO) is implicated in both acute effects of addictive drugs and development of dependence to them. We investigated the role of NO in nicotine-induced locomotor sensitization.
The effects of Nω-nitro-l-arginine methyl ester (l-NAME), a NO synthase inhibitor, and a combination of a NO precursor l-arginine and l-NAME on nicotine-induced locomotor sensitization were investigated in Swiss Webster mice.
Sensitization to psychomotor stimulating effect of nicotine was rendered by seven injections of nicotine (1 mg/kg) on every other day. To investigate their effect on the development of sensitization to nicotine, l-NAME (15–60 mg/kg) and l-arginine (1 g/kg) were given before nicotine administration during the first seven sessions. To investigate the effect of these compounds on the expression of nicotine sensitization, after a 4-day drug-free period another group of mice received a challenge injection of nicotine on day 18.
Nicotine (1 mg/kg) produced a robust locomotor sensitization in mice. The doses of 30 mg/kg and 60 mg/kg of l-NAME blocked the development of sensitization to nicotine; and, l-arginine (1 g/kg) pretreatment reversed this effect of l-NAME. Likewise, the doses of 30 mg/kg and 60 mg/kg of l-NAME inhibited the expression of sensitization to nicotine on day 18; and, l-arginine (1 g/kg) pretreatment reversed this inhibitory effect of l-NAME.
Our results suggest that NO is implicated in the development and expression of nicotine-induced locomotor sensitization in mice.
KeywordsLocomotor sensitization l-NAME l-Arginine Nicotine Nitric oxide Mice
This study was supported by the State Planning Institution and Ministry of Defense of the Turkish Government (Grant No: MSB-3, 99K120150).
- Bredt DS, Snyder SH (1992) Nitric oxide, a novel neuronal messenger. Neuron 8:3–11Google Scholar
- Bryne G (1988) Nicotine likened to cocaine, heroine. Science 240:1143Google Scholar
- Çelik T, Zağlı Ü, Kayir H, Uzbay IT (1999) Nitric oxide synthase inhibition blocks amphetamine-induced locomotor activity in mice. Drug Alcohol Depend 56:109–113Google Scholar
- Domino EF (2001) Nicotine induced behavioral locomotor sensitization. Prog Neuropsychopharmacol Biol Psychiatry 25:59–71Google Scholar
- Gerdeman GL, Partridge JG, Lupica CR, Lovinger DM (2003) It could be habit forming: drugs of abuse and striatal synaptic plasticity. Trends Neurosci 26:184–192Google Scholar
- Koob GF, Le Moal M (1997) Drug abuse: hedonic homeostatic dysregulation. Science 279:52–58Google Scholar
- Malin DH, Lake JR, Shenoi M, Upchurch TP, Johnson SC, Schweinle WE, Cadle CD (1998) The nitric oxide synthesis inhibitor nitro-l-arginine (l-NNA) attenuates nicotine abstinence syndrome in the rat. Psychopharmacology 140:371–377Google Scholar
- Miller DK, Wilkins LH, Bardo MT, Crooks PA, Dwoskin LP (2001) Once weekly administration of nicotine produces long-lasting locomotor sensitization in rats via a nicotinic receptor-mediated mechanism. Psychopharmacology 156:469–476Google Scholar
- Miller DK, Harrod SB, Green TA, Wong MY, Bardo MT, Dwoskin LP (2003) Lobeline attenuates locomotor stimulation induced by repeated nicotine administration in rats. Pharmacol Biochem Behav 74:279–286Google Scholar
- Ohno M, Watanabe S (1995) Nitric oxide synthase inhibitors block behavioral sensitization to methamphetamine in mice. Eur J Pharmacol 275:39–44Google Scholar
- Pogun S, Demirgoren S, Taskiran D, Kanit L, Yilmaz O, Koylu EO, Balkan B, London ED (2000) Nicotine modulates nitric oxide in rat brain. Eur Neuropsychopharmacol 10:463–472Google Scholar
- Pointieri FE, Tanda G, Di Chiara G (1996) Effects of nicotine on the nucleus accumbens and similarity to those of addictive drugs. Nature 382:255–258Google Scholar
- Przegalinski E, Filip M (1997) Nitric oxide (NO) pathway and locomotor hyperactivity towards dopaminomimetics in rats. Pol J Pharmacol 49:291–298Google Scholar
- Pudiak CM, Bozarth MA (1993) l-NAME and MK-801 attenuate sensitization to the locomotor-stimulating effect of cocaine. Life Sci 53:1517–1524Google Scholar
- Robinson TE, Berridge KC (1993) The neural basis of drug craving: an incentive-sensitization theory of addiction. Brain Res Rev 18:247–291Google Scholar
- Robinson TE, Berridge KC (2000) The psychology and neurobiology of addiction: an incentive-sensitization view. Addiction 95(Suppl 2):S91–S118Google Scholar
- Shim I, Javaid JL, Wirtshafter D, Jang SY, Shin KY, Lee HJ, Chung YC, Chun BG (2001) Nicotine-induced behavioral sensitization is associated with extracellular dopamine release and expression of c-Fos in the striatum and nucleus accumbens of the rat. Behav Brain Res 121:137–147Google Scholar
- Shim I, Kim HT, Kim YH, Chun BG, Hahm DH, Lee EH, Kim SE, Lee HJ (2002) Role of nitric oxide synthase inhibitors and NMDA receptor antagonist in nicotine-induced behavioral sensitization in the rat. Eur J Pharmacol 443:119–124Google Scholar
- Suemaru K, Kawasaki H, Gomita Y, Tanizaki Y (1997) Involvement of nitric oxide in development of tail-tremor induced by repeated nicotine administration in rats. Eur J Pharmacol 335:139–143Google Scholar
- Uzbay IT (2001) l-NAME precipitates catatonia during ethanol withdrawal in rats. Behav Brain Res 119:71–76Google Scholar
- Uzbay IT, Kayir H (2003) Bromocriptine and quinpirole, but not 7 OH-DPAT or SKF 38393, potentiate the inhibitory effect of l-NAME on ethanol-induced locomotor activity in mice. Naunyn Schmiedeberg’s Arch Pharmacol 367:414–421Google Scholar
- Uzbay IT, Oglesby MW (2001) Nitric oxide and substance dependence. Neurosci Biobehav Rev 25:43–52Google Scholar