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  • Notwithstanding the functioning of galaninergic system may


    Notwithstanding, the functioning of galaninergic system may be even more complex (Fuxe et al., 2012). Some studies present evidence that GAL2 receptors might form heteroreceptor complexes with neuropeptide Y1 receptors in AZ191 of amygdala (Narváez et al., 2015a), DRN (Díaz-Cabiale et al., 2011) and also of hippocampus (Narváez et al., 2015b). Apparently, when GAL2 receptors from the GAL2/NPYY1 heteroreceptor complexes were activated, at least in the amygdala, they switch from a Gq to a Gi/o coupling (Narváez et al., 2015a). GAL1 and GAL2 may also form heteroreceptor complexes with 5-HT1A receptors in vitro (Borroto-Escuela et al., 2010) and in the dorsal hippocampus (Millón et al., 2015). Then, the anxiogenic-like effect of galanin in the dorsal hippocampus noticed in the present work might be due to a complex interaction between different receptors. We employed the EPM as a tool to evaluated anxiety-like behaviours in animals treated with intra-dorsal hippocampal galanin ligands. The behaviours exhibited by rats in the EPM are easily reproduced, allowing to perform quickly a set of pharmacological experiments to detect both anxiogenic and anxiolytic-like effect of drugs (Cipriano et al., 2016, Duarte et al., 2016, Griebel and Holmes, 2013, Kshama et al., 1990, Rodgers and Dalvi, 1997). Beyond the predictive validity of EPM, some studies also used this paradigm to showed the involvement of dorsal hippocampus on unconditioned anxiety-like behaviours by different neurotransmitters/neuromodulators (Ashabi et al., 2011, Canto-de-Souza et al., 2015, Piri et al., 2012, Zarrindast et al., 2011). On the other hand, some authors have discussed if the EPM elicits only unlearned anxiety (Carobrez and Bertoglio, 2005). In this line, one limitation of our study is that we did not investigate the galanin effects on different paradigms of anxiety. According to our observations, injection of galanin within the dorsal hippocampus induced anxiogenic-like behaviours in rats. The anxiogenic-like effect of galanin in the dorsal hippocampus seems to be tonic, since blocking GAL2 receptors provoked the opposite effect. As pointed before, the anxiogenic-like effect of galanin was counteracted by pretreatment with a GAL2 antagonist, supporting the putative role of GAL2 receptors on this effect of galanin mediated by the dorsal hippocampus.
    Experimental procedure
    Introduction Throughout the world, alcoholic drinks are extensively consumed and while most adults drink at levels of low-risk, there are many that undertake harmful or hazardous drinking. Globally, 3.3 million lives are lost every year from alcohol related issues, accounting for 5.1% of the overall disease burden (Poznyak et al., 2014). Similarly, opioid abuse and dependency is a major problem globally with reports that approximately 32 million adults use opioids and 16 million use opiates; a stable global figure (UNOCD, 2015). The availability of prescription opioids like oxycodone and lack of education about the abuse potential of these drugs has fuelled the increased incidence of addiction. Furthermore, nearly half of young adults who inject heroin reported abusing prescription opioids before starting heroin use (NIDA, 2014). While there are a range of medicines available to treat both AUD (Chick et al., 1992, De Witte et al., 2005, Johnson et al., 2000, Johnson et al., 2002, Sinclair, 2001, Tambour and Quertemont, 2007), and opiate dependency (Cornish et al., 1997, Joseph et al., 1999, Walsh et al., 1994) many of the current treatments are inadequate in regard to efficacy, tolerance, side effects and compliance, and the incidence of alcohol and opioid use remains high. There is abundant literature on the mesocorticolimbic dopamine system and its role in mediating the reinforcing effects of ethanol and opioids (Everitt and Robbins, 2005, Kalivas, 2009, Koob and Volkow, 2010). The complex chain of neurobiological events accountable for the development and persistence of drug dependency offer a variety of targets for pharmacotherapies. There is anatomical overlap in expression of neuropeptides, including galanin, with brain regions of the mesolimbic dopamine system and hence galanin has been identified as a novel therapeutic target for drug addiction (Kaplan et al., 1988, Melander et al., 1986a, Melander et al., 1986b, Skofitsch and Jacobowitz, 1986). Galanin is a small highly conserved 29 amino acid neuropeptide (30 amino acids in humans) that is recognized as a promising target to treat alcoholism (Ash et al., 2011, Rada et al., 2004), opioid dependency (Holmes et al., 2012) and mood disorders including depression (Barr et al., 2006, Saar et al., 2013) and anxiety (Lu et al., 2007). Galanin has a broad distribution in both the peripheral and central nervous systems and is co-localised with a number of classical neurotransmitters and other neuropeptides. Due to this wide-ranging expression, galanin is widely implicated in numerous biological processes ranging from learning and memory, nociception and feeding behaviour (Lang et al., 2015).