ABSTRACT
Title
Mining the serotonin 5-HT2C receptors and their ligands in drug addiction
Authors
M. Filip1,2, M. Zaniewska1
1Laboratory of Drug Addiction Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland
2Department of Toxicology, Faculty of Farmacy, Jagiellonian University, College of Medicine, Kraków, Poland
1Laboratory of Drug Addiction Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland
2Department of Toxicology, Faculty of Farmacy, Jagiellonian University, College of Medicine, Kraków, Poland
Abstract
Serotonin (5-HT) neurotransmission controls the brain physiology and contributes to the etiology of many neuropsychiatric disorders [1]. One of the key modulators of 5-HT system are 5-HT2C receptors which regulate feeding, satiety, mood and cognition as well as underline the mechanisms of depression, schizophrenia and addiction [2] Regarding the latter disease, preclinical studies have revealed a significant inhibitory potential for 5-HT2C receptor agonists to control several responses evoked by psychostimulant drugs of abuse [2]. Growing evidence supports also a role of 5-HT2C receptors in modulating responses to nicotine, one of the key psychoactive components of tobacco smoke.
The present series of studies investigated the effects of 5-HT2C receptor ligands on the behavioral responses to nicotine in rats. We demonstrated that 5-HT2C receptors play a pivotal role in the acute effects of nicotine, while following repeated intermittent administration of nicotine 5-HT2C receptor activation decreases both the response to acute nicotine and nicotine-induced conditioned hyperactivity. Furthermore, 5-HT2C receptors do not play a permissive role in the development of nicotine sensitization, although their activation was essential for the expression of nicotine sensitization [3]. None of 5-HT2C receptor ligands administered during the second withdrawal period of nicotine-treated rats altered the locomotor effect of nicotine given on day 15. Nicotine withdrawal, associated by affective symptoms leading to relapse, in animals seen as the depression-like effects was abolished by pretreatment with 5-HT2C receptor agonists [4].
Concluding, pharmacological stimulation of 5-HT2C receptors play an essential inhibitory role in behavioral effects of nicotine.Obtained data show a new direction in the search for efficient anti-addictive drugs and the possibility of using 5-HT2C receptor agonists in the pharmacotherapy of nicotine addiction, as an adjunct to smoking cessation therapies.
References
[1] Filip M., Bader M.Pharmacol. Rep., 2009, 61, 761-777.
[2] Filip M, Alenina N, Bader M, Przegaliński E. Addiction Biology, 2010,. 15, 227-249.
[3] Zaniewska M, McCreary AC, Wydra K, Filip M. Neuropharmacology, 2010, 58, 1140-1146.
[4] Zaniewska M, McCreary AC, Wydra K, Filip M. Synapse, 2010, 64, 511-519.
The present series of studies investigated the effects of 5-HT2C receptor ligands on the behavioral responses to nicotine in rats. We demonstrated that 5-HT2C receptors play a pivotal role in the acute effects of nicotine, while following repeated intermittent administration of nicotine 5-HT2C receptor activation decreases both the response to acute nicotine and nicotine-induced conditioned hyperactivity. Furthermore, 5-HT2C receptors do not play a permissive role in the development of nicotine sensitization, although their activation was essential for the expression of nicotine sensitization [3]. None of 5-HT2C receptor ligands administered during the second withdrawal period of nicotine-treated rats altered the locomotor effect of nicotine given on day 15. Nicotine withdrawal, associated by affective symptoms leading to relapse, in animals seen as the depression-like effects was abolished by pretreatment with 5-HT2C receptor agonists [4].
Concluding, pharmacological stimulation of 5-HT2C receptors play an essential inhibitory role in behavioral effects of nicotine.Obtained data show a new direction in the search for efficient anti-addictive drugs and the possibility of using 5-HT2C receptor agonists in the pharmacotherapy of nicotine addiction, as an adjunct to smoking cessation therapies.
References
[1] Filip M., Bader M.Pharmacol. Rep., 2009, 61, 761-777.
[2] Filip M, Alenina N, Bader M, Przegaliński E. Addiction Biology, 2010,. 15, 227-249.
[3] Zaniewska M, McCreary AC, Wydra K, Filip M. Neuropharmacology, 2010, 58, 1140-1146.
[4] Zaniewska M, McCreary AC, Wydra K, Filip M. Synapse, 2010, 64, 511-519.