nACHRs are highly distributed in the CNS and promote the release of not only acetylcholine (ACh) but also DA, NA, 5-HT and gamma-aminobutiric acid (GABA) ( Wonnacott et al., 2005). Moreover, MDMA has affinity for neuronal nicotinic acetylcholine receptors (nAChRs) and acts as a partial agonist of alpha7 nAChR ( Chipana et al., 2008 Garcia-Ratés et al., 2010). Aforementioned mechanisms lead to the extracellular increase of neurotransmitters level in CNS (for review see Budzynska et al., 2017). MDMA also delays metabolism by inhibiting monoamine oxidase (MAO) and binds to distinct 5-HT and NA receptors ( Leonardi and Azmitia, 1994 White et al., 1996 Capela et al., 2009). MDMA is able to elevate dopamine (DA) and noradrenaline (NA) levels, although this effect is less pronounced. This process is supposed to be a presumable mechanism contributing to 5-HT release, the main pharmacological effect of MDMA. It is well established that MDMA by itself reduced the activity of serotonin (5-HT) transporters in the brain. Data on behavioral effects of concomitant administration of MDMA and nicotine are also scarce. ![]() Hence, nicotine present in tobacco may modulate the behavioral and neurochemical effects of MDMA in real-life situations.Īlthough the acute and chronic effects of MDMA in animal models have been widely described ( Navarro and Maldonado, 2002 Cole and Sumnall, 2007 Viñals et al., 2013), very few studies have evaluated the consequences of polydrug associations. In fact, abuse of MDMA by tobacco smokers has been commonly reported, especially in a nightclub setting ( Mohamed et al., 2011 UNODC World Drug Report, 2010) 1. ![]() A significant issue related to the MDMA abuse is the co-administration of MDMA with other stimulants: ethanol, amphetamines, cocaine, cannabis or nicotine (UNODC World Drug Report. Illicit MDMA is typically manufactured in a form of tablets of varying purity, with ketamine, amphetamine and caffeine being the most common contaminants ( Tanner-Smith, 2006). It also induces neurotoxicity ( Gonçalves et al., 2014). MDMA is a stimulant of the central nervous system (CNS) possesses hallucinogenic properties described as an increased sensory awareness ( Morton, 2005 George et al., 2010). Such abuse results in fatal cases especially among young people. Both drugs are very often used in combination, especially by young people, thus these results may help explaining why psychoactive substances are being co-abused and why this polydrug administration is still a social problem.ģ,4-Methylenedioxy-methylamphetamine (MDMA), a synthetic substance well known as ecstasy, is a worldwide recreational drug of abuse. Our study showed for the first time strong behavioral and biochemical interactions between nicotine and MDMA. Furthermore, one of the main findings of the present study is that MDMA increased locomotor activity in nicotine-sensitized mice. ![]() The results revealed that MDMA injections as well as co-administrations of MDMA and nicotine improved memory consolidation in male Swiss mice tested in PA task. Also, the oxidative stress parameters as well as expression levels of α7 nAChRs in prefrontal cortex and hippocampus of mice treated with MDMA alone or in combination with nicotine were assessed. For behavioral study the passive avoidance (PA) test and locomotor sensitization paradigm were used. As MDMA and nicotine activate the same neuronal pathways, we examined the influence of co-administration of nicotine (0.05 mg/kg) and MDMA (1 mg/kg) on cognitive processes, nicotine-induced behavioral sensitization and on processes linked with oxidative stress and α7 nicotinic acetylcholine receptors (nAChRs) expression in the brain of male Swiss mice. 3Department of Medical Chemistry, Medical University of Lublin, Lublin, Polandģ,4-Methylenedioxy-methylamphetamine (MDMA), a synthetic substance commonly known as ecstasy, is a worldwide recreational drug of abuse.2Department of Biopharmacy, Medical University of Lublin, Lublin, Poland.1Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, Lublin, Poland.Barbara Budzynska 1 *, Artur Wnorowski 2, Katarzyna Kaszubska 1, Grazyna Biala 1, Marta Kruk-Słomka 1, Jacek Kurzepa 3 and Anna Boguszewska-Czubara 3
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