• 2018-07
  • 2019-04
  • 2019-05
  • 2019-06
  • 2019-07
  • 2019-08
  • β-Sitosterol Social interaction is known to be the main


    Social interaction is known to be the main source of stress in human beings (Dickerson and Kemeny, 2004, Tamashiro et al., 2005). An animal model of social stress should closely mimic real-life situations in human life (Neisewander et al., 2012); in this context, social defeat in an agonistic encounter between rodents is a model of ecological validity for recreating experiences such as bullying, physical abuse or subordination stress (Björkqvist, 2001; Lu et al., 2003; Miczek et al., 2008; Tornatzky and Miczek, 1993). After being exposed to repeated social defeat, rodents show a range of depression-like symptoms such as anhedonia, social withdrawal and metabolic syndrome (weight gain and insulin and leptin resistance) (Meerlo et al., 1996, Von Frijtag et al., 2000). It has repeatedly been shown that exposure to different procedures of social defeat increases the rewarding and reinstating effects of psychostimulant drugs, such as cocaine, in the self-administration (SA) and conditioned place preference (CPP) paradigms (Aguilar et al., 2013, vington et al., 2008, Neisewander et al., 2012). Defeated animals also show an enhanced sensitivity to cocaine-induced hyperactivity (Nikulina et al., 1998, Nikulina et al., 2004) and dopaminergic cross-sensitization, with an augmented behavioral response to subsequent doses of cocaine after repeated drug exposure (Kalivas et al., 1998, Piazza and Le Moal, 1998, Steketee and Kalivas, 2011). These effects are associated with increased dopamine transmission in the corticolimbic system (Steketee and Kalivas, 2011), including projections from the ventral tegmental area to the medial prefrontal β-Sitosterol and the nucleus accumbens (Pierce and Kalivas, 1997, Steketee and Kalivas, 2011), which are the main structures implicated in the rewarding and motor effects of psychostimulants (Koob, 2009, Sinha, 2008). These changes in the corticolimbic system may be mediated by the action of neuropeptide corticotropin-releasing factor (CRF), which interacts with two G-protein-coupled corticotropin-releasing factor CRF receptors, type 1 (corticotropin-releasing factor CRF1 receptor) and type 2 (corticotropin-releasing factor CRF2 receptor), both positively coupled to adenylate cyclase through stimulatory G-proteins (Binder and Nemeroff, 2010, Hauger et al., 2009, Zorrilla and Koob, 2004, Zorrilla and Koob, 2010) with actions at central and peripheral levels (Hauger et al., 2006, Heinrichs and Koob, 2004). This factor is known as the principal mediator of a wide range of both acute and chronic neuroendocrine and behavioral responses to stress (Logrip et al., 2011). Corticotropin-releasing factor activates the hypothalamic-pituitary-adrenal axis and stimulates the release of glucocorticoids (Bale and Vale, 2004). In addition, corticotropin-releasing factor axons project to extrahypothalamic areas such as the extended amygdala and ventral tegmental area, thereby modulating dopamine function and causing neuroadaptations in dopamine neurons in the corticolimbic pathway (Haass-Koffler and Bartlett, 2012, Saal et al., 2003, Wanat et al., 2008). This especially relevant during withdrawal (Zorrilla et al., 2014), when corticotropin-releasing factor plays a key role in anxiety-like effects and helps to explain the negative reinforcement processes that drive the compulsivity of addiction (Koob, 2008). The aim of this investigation was to study the role of both corticotropin-releasing factor receptors in the effects of social stress on the conditioned rewarding effects and locomotor sensitization induced by cocaine. To achieve our objective, we administrated a pretreatment of a peripheral injection of the nonpeptidic corticotropin-releasing factor CRF1 receptor antagonist CP-154,526 or the peptidic corticotropin-releasing factor CRF2 receptor antagonist Astressin2-B before each social defeat. It should be noticed that corticotropin-releasing factor CRF1 and 2 antagonists were injected peripherally. As CP-154,526 crosses the blood brain barrier we expected it to block central and peripheral corticotropin-releasing factor CRF1 receptors. On the other hand, Astressin2-B acts only on peripheral corticotropin-releasing factor CRF2 receptors such as those located on the pituitary and other peripheral locations.