Social Interaction and Cocaine Conditioning in Mice Increase Spontaneous Spike Frequency in the Nucleus Accumbens or Septal Nuclei as Revealed by Multielectrode Array Recordings

Abstract

Both cocaine and social interaction place preference conditioning lead to increased neuronal expression of the immediate early gene EGR1 in the nucleus accumbens, a central region of the reward pathway, suggesting that both drug and natural rewards may be processed in similar brain regions. In order to gain novel insights into the intrinsic in vitro electrical activity of the nucleus accumbens and adjacent brain regions and to explore the effects of reward conditioning on network activity, we performed multielectrode array recordings of spontaneous firing in acute brain slices of mice conditioned to either cocaine or social interaction place preference. Cocaine conditioning increased the spike frequency of neurons in the septal nuclei, whereas social interaction conditioning increased the spike frequency in the nucleus accumbens compared to saline control animals. In addition, social interaction conditioning decreased the amount of active neuron clusters in the nucleus accumbens. Our findings suggest that place preference conditioning for both drug and natural rewards may induce persistent changes in neuronal network activity in the nucleus accumbens and the septum that are still preserved in acute slice preparations.

Dyadic social interaction inhibits cocaine-conditioned place preference and the associated activation of the accumbens corridor

“…Thus, the EGR1 and c-Fos activation patterns observed immunohistochemically ( Prast et al 2014a , 2014b ) strongly support the concept of a ventromedial to dorsolateral striatal gradient with respect to the expression of behavior motivated by drugs of abuse, particularly cocaine ( Voorn et al , 2004 ; Ikemoto, 2007 ; Haber and Knutson, 2010 ). In contrast, our electrophysiologic [multielectrode array (MEA)] findings ( Kummer et al , 2015 , discussed below) and our lesion study ( Fritz et al , 2011a ) are more difficult to interpret according to this gradient concept.…”

“…1 for the individual animals’ behavior), with both mice and rats starting the experiment at an age of 6–8 weeks and both conspecifics being of the male sex. In a subsequent study ( Kummer et al , 2015 ), the percentage of C57BL/6N mice developing aversion to social interaction increased to 42% (five of 12). As our experimental database for C57BL/6 mice grows and the number of different experimenters increases, the overall percentage of mice that develop CPA to DSI is shifting more toward 50%.…”

“…Finally, despite all the shortcomings and caveats and open questions discussed above, we could successfully use our experimental models to answer a number of questions on DSI versus cocaine reward ( Fritz et al , 2011a , 2011b , 2011c ; Kummer et al , 2011 , 2014 , 2015 ; Zernig et al , 2011 ; El Rawas et al , 2012a , 2012b ; Prast et al , 2012 , 2014b ) and to investigate the neural basis for the increased cocaine CPP shown by animals bred for high anxiety ( Prast et al , 2014a ).…”

Sex-dependent regulation of social reward by oxytocin: an inverted U hypothesis

“…OT AND SOCIAL REWARD-ANIMAL STUDIES OT in the mesolimbic dopamine system There is strong support for the role of OT in regulating social reward by its actions in the mesolimbic dopamine system. This system is critical for the rewarding properties of many stimuli, including food [83], water [84], drugs of abuse, and various social interactions [85][86][87]. The primary pathway of the mesolimbic circuitry is dopamine (DA)-containing neurons in the ventral tegmental area (VTA) that project to the NAc [88][89][90].…”

“…The primary pathway of the mesolimbic circuitry is dopamine (DA)-containing neurons in the ventral tegmental area (VTA) that project to the NAc [88][89][90]. Social interactions can increase neuronal activity in both the VTA and NAc in male hamsters, rats, and mice [8,85,91], and selective activation of this DA projection increases social motivation in mice [87]. Indeed, the activation of OTRs in the mesolimbic circuit appears to be necessary for social interactions to be rewarding in male rodents.…”