Late decrease of pCREB in the Basolateral Amygdala by Social Interaction Reward
Journal Title: Biomedical Journal of Scientific & Technical Research (BJSTR) - Year 2018, Vol 19, Issue 4
Abstract
Background: The transcription factor CREB (cAMP response element-binding protein) has been shown to be activated by drugs of abuse in reward-related brain regions. However, the effects of natural reward on CREB activation are under-investigated. Here we investigated the effects of social interaction conditioned place preference (CPP) on CREB phosphorylation at two different time points (early 1 hour and late 24 hours after the CPP test) in various brain regions involved in reward and stress-reactions of 1) rats that express social interaction CPP or 2) control saline rats that received saline in both compartments of the CPP apparatus. Finding: We found that social interaction CPP did not alter CREB activation 1 hour after the CPP test but decreased CREB phosphorylation 24 hours after the CPP test, specifically in the basolateral amygdala. Conclusion: As stress increases CREB activation in several brain regions including the basolateral amygdala, these results confirm our previous finding that social interaction.The transcription factor CREB, upon phosphorylation on Ser 133, activates gene expression by binding CRE elements in promoter regions of other proteins and transcription factors that mediate neural plasticity Berke et al. [1,2]. Drugs of abuse activate CREB in several reward-related brain regions such as the ventral tegmental area, the amygdala and the frontal cortex Hyman et al. [3]. Specifically, cocaine conditioned place preference was found to increase CREB phosphorylation in the nucleus accumbens Tropea et al. [4] core but not the shell subregion Miller et al. [5]. Viral-mediated overexpression of CREB in the nucleus accumbens shell and core (effect more pronounced in the shell of the nucleus accumbens) decreases the rewarding effects of cocaine and makes low doses of the drug aversive. Conversely, overexpression of a dominant-negative mutant CREB increases the rewarding effects of cocaine Carlezon et al. [6,7]. In parallel, it has been shown that mice with a mutation in the α and Δ isoforms of the CREB gene demonstrate an enhanced response to the rewarding properties of cocaine compared with their wild-type controls in conditioned place preference Walters et al. [8]. However, a study has shown that CREB activity in the nucleus accumbens shell increases cocaine reinforcement in self-administering rats Larson et al. [9]. While the effects of drugs, particularly cocaine conditioned place preference on CREB activation have been widely addressed, the ability of natural reward-related stimuli to promote CREB activation has not been well examined. It has been reported that tone stimuli associated with sucrose food pellets natural reward increased CREB phosphorylation in the nucleus accumbens shell and core Shiflett et al. [10]. In addition, functional studies have shown that viral mediated overexpression of CREB in the nucleus accumbens shell also affected the preference for sucrose Barrot et al. [11]. Positive social experience outside the drug context may serve as an alternative to drug taking Kummer et al. [12,13]. As for drugs of abuse, positive social interaction is rewarding and social reward can be assessed by applying the conditioned place preference paradigm (CPP) El Rawas et al. [13]. Rats acquired robust CPP to either cocaine alone or social interaction alone Fritz et al. [14-16]. reward may have anti-stress effects.
Authors and Affiliations
Ahmad Salti, Rana El Rawas
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