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Blockade of alcohol-induced locomotor sensitization and conditioned place preference in DBA mice by 7-nitroindazole
1Department of Psychiatry and Behavioral Science (R-629), Room 503, Gautier Building, University of Miami School of Medicine, Miami, FL 33101, USA. yitzhak@mednet.med.miami.edu
Abstract:
Our previous studies indicated that inhibition or ablation of the neuronal nitric oxide synthase (nNOS) prevents the development of sensitization to the locomotor-stimulating effect of cocaine and cocaine-induced conditioned place preference (CPP). The present study was undertaken to investigate the effect of the nNOS inhibitor, 7-nitroindazole (7-NI), on ethanol-induced locomotor sensitization and CPP in DBA/2J mice. Administration of ethanol (1.5 g/kg; i.p.) for 7 days resulted in a progressive increase in the locomotor-stimulating effect of ethanol. Pretreatment with 7-NI (25 mg/kg) blocked the expression of the sensitized response to ethanol. A challenge injection of ethanol given 1 week and then 4 weeks following withdrawal from ethanol indicated that (a) ethanol sensitization was long lasting, and (b) the co-administration of 7-NI and ethanol attenuated the sensitized response to ethanol challenge. The CPP experiments showed that pairing four ethanol (2.5 g/kg) injections with a specific environment resulted in a marked preference for the drug-paired environment. The pretreatment with 7-NI (25 mg/kg) completely blocked ethanol-induced CPP. 7-NI alone produced neither rewarding nor aversive effects. Taken together, results of the present study indicate that blockade of nNOS by 7-NI-attenuated ethanol-induced behavioral sensitization and completely blocked the rewarding effect of ethanol. These findings support the role of NO in ethanol actions and further suggest that the nNOS system is relevant to the rewarding effects of various drugs of abuse.
Insights
Inhibiting neuronal nitric oxide synthase (nNOS) with 7-nitroindazole (7-NI) blocked ethanol-induced locomotor sensitization and rewarding effects in mice. This highlights nNOS
Area of Science:
- Neuroscience
- Pharmacology
- Addiction Research
Background:
- Neuronal nitric oxide synthase (nNOS) inhibition previously prevented cocaine sensitization and conditioned place preference (CPP).
- The role of nNOS in ethanol's effects, particularly sensitization and reward, requires further investigation.
Purpose of the Study:
- To investigate the impact of the nNOS inhibitor 7-nitroindazole (7-NI) on ethanol-induced locomotor sensitization and CPP in DBA/2J mice.
Main Methods:
- Mice received daily ethanol injections (1.5 g/kg) for 7 days to induce locomotor sensitization.
- 7-NI (25 mg/kg) was administered as a pretreatment to assess its effect on ethanol sensitization and CPP.
- Ethanol-induced CPP was established by pairing drug injections with a specific environment.
Main Results:
- Ethanol administration led to progressive locomotor sensitization, which was blocked by 7-NI pretreatment.
- Ethanol sensitization was long-lasting, and 7-NI attenuated the response to challenge injections weeks after withdrawal.
- 7-NI completely blocked ethanol-induced CPP, while 7-NI alone had no significant effects.
Conclusions:
- Blockade of nNOS by 7-NI attenuates ethanol-induced behavioral sensitization and completely blocks its rewarding effects.
- These findings support a role for nitric oxide (NO) in mediating ethanol's actions.
- The nNOS system is implicated in the rewarding effects of various drugs of abuse.