Chronic treatment with the vasopressin 1b receptor antagonist SSR149415 prevents the dysphoria associated with nicotine withdrawal in rats
- PMID: 26112757
- PMCID: PMC4558258
- DOI: 10.1016/j.bbr.2015.06.031
Chronic treatment with the vasopressin 1b receptor antagonist SSR149415 prevents the dysphoria associated with nicotine withdrawal in rats
Abstract
Nicotine addiction is a chronic brain disorder that is characterized by dysphoria upon smoking cessation and relapse after brief periods of abstinence. It has been hypothesized that the negative mood state associated with nicotine withdrawal is partly mediated by a heightened activity of brain stress systems. Animal studies suggest that blockade of vasopressin 1b (V1b) receptors diminishes high levels of drug intake in dependent animals and attenuates the emotional response to stressors. The goal of the present studies was to investigate the effect of acute and chronic treatment with the V1b receptor antagonist SSR149415 on the negative mood state associated with nicotine withdrawal in rats. An intracranial self-stimulation (ICSS) procedure was used to assess mood states and nicotine dependence was induced using minipumps. The nicotinic receptor antagonist mecamylamine was used to precipitate withdrawal. Mecamylamine elevated the brain reward thresholds of the nicotine dependent rats, which reflects a negative mood state. Mecamylamine did not affect the brain reward thresholds of the saline-treated control rats. Chronic treatment with SSR149415 completely prevented the elevations in brain reward thresholds associated with nicotine withdrawal while acute treatment only partly prevented nicotine withdrawal. These data suggest that chronic treatment with V1b receptor antagonists may prevent the dysphoria associated with smoking cessation and thereby improve relapse rates.
Keywords: Dysphoria; ICSS; Nicotine; SSR149415; Vasopressin 1b receptor; Withdrawal.
Published by Elsevier B.V.
Figures
![Figure 1](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/4558258/bin/nihms-707380-f0001.gif)
![Figure 1](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/4558258/bin/nihms-707380-f0001.gif)
![Figure 2](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/4558258/bin/nihms-707380-f0003.gif)
![Figure 2](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/4558258/bin/nihms-707380-f0003.gif)
Similar articles
-
Blockade of CRF1 receptors in the central nucleus of the amygdala attenuates the dysphoria associated with nicotine withdrawal in rats.Pharmacol Biochem Behav. 2012 Mar;101(1):62-8. doi: 10.1016/j.pbb.2011.12.001. Epub 2011 Dec 9. Pharmacol Biochem Behav. 2012. PMID: 22182462 Free PMC article.
-
Sex differences in the reward deficit and somatic signs associated with precipitated nicotine withdrawal in rats.Neuropharmacology. 2019 Dec 1;160:107756. doi: 10.1016/j.neuropharm.2019.107756. Epub 2019 Sep 2. Neuropharmacology. 2019. PMID: 31487496 Free PMC article.
-
Overexpression of CRF in the BNST diminishes dysphoria but not anxiety-like behavior in nicotine withdrawing rats.Eur Neuropsychopharmacol. 2016 Sep;26(9):1378-1389. doi: 10.1016/j.euroneuro.2016.07.007. Epub 2016 Jul 22. Eur Neuropsychopharmacol. 2016. PMID: 27461514 Free PMC article.
-
Neuropeptide systems and new treatments for nicotine addiction.Psychopharmacology (Berl). 2017 May;234(9-10):1419-1437. doi: 10.1007/s00213-016-4513-5. Epub 2016 Dec 28. Psychopharmacology (Berl). 2017. PMID: 28028605 Free PMC article. Review.
-
An overview of SSR149415, a selective nonpeptide vasopressin V(1b) receptor antagonist for the treatment of stress-related disorders.CNS Drug Rev. 2005 Spring;11(1):53-68. doi: 10.1111/j.1527-3458.2005.tb00035.x. CNS Drug Rev. 2005. PMID: 15867952 Free PMC article. Review.
Cited by
-
Methylation of the Oxytocin, Oxytocin Receptor, and Vasopressin Gene Promoters in Tobacco Use Disorder during Cessation.Neuropsychobiology. 2024;83(1):28-40. doi: 10.1159/000535663. Epub 2024 Jan 5. Neuropsychobiology. 2024. PMID: 38185116 Free PMC article.
-
The Role of Oxytocin and Vasopressin in Drug-Induced Reward-Implications for Social and Non-Social Factors.Biomolecules. 2023 Feb 21;13(3):405. doi: 10.3390/biom13030405. Biomolecules. 2023. PMID: 36979340 Free PMC article. Review.
-
Self-administration of the synthetic cathinone MDPV enhances reward function via a nicotinic receptor dependent mechanism.Neuropharmacology. 2018 Jul 15;137:286-296. doi: 10.1016/j.neuropharm.2018.05.008. Epub 2018 May 9. Neuropharmacology. 2018. PMID: 29778945 Free PMC article.
-
Involvement of Activated Brain Stress Responsive Systems in Excessive and "Relapse" Alcohol Drinking in Rodent Models: Implications for Therapeutics.J Pharmacol Exp Ther. 2018 Jul;366(1):9-20. doi: 10.1124/jpet.117.245621. Epub 2018 Apr 18. J Pharmacol Exp Ther. 2018. PMID: 29669731 Free PMC article. Review.
-
V1b Receptor Antagonist SSR149415 and Naltrexone Synergistically Decrease Excessive Alcohol Drinking in Male and Female Mice.Alcohol Clin Exp Res. 2018 Jan;42(1):195-205. doi: 10.1111/acer.13544. Epub 2017 Nov 28. Alcohol Clin Exp Res. 2018. PMID: 29105118 Free PMC article.
References
-
- WHO WHO global report on trends in tobacco smoking 2000-2025. 2015.
-
- Postma DS, Bush A, van den Berge M. Risk factors and early origins of chronic obstructive pulmonary disease. Lancet. 2015;385:899–909. - PubMed
-
- Ott A, Slooter AJ, Hofman A, van Harskamp F, Witteman JC, Van Broeckhoven C, et al. Smoking and risk of dementia and Alzheimer's disease in a population-based cohort study: the Rotterdam Study. Lancet. 1998;351:1840–3. - PubMed
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources