Neurotransmitter Genes in the Nucleus Accumbens That Are Involved in the Development of a Behavioral Pathology After Positive Fighting Experiences and Their Deprivation: A Conceptual Paradigm for Data Analysis

It has been shown previously that repeated positive fighting experience in daily agonistic interactions is accompanied by the development of psychosis-like behavior, with signs of an addiction-like state associated with changes in the expression of genes encoding the proteins involved in the main neurotransmitter events in some brain regions of aggressive male mice. Fighting deprivation (a no-fight period of 2 weeks) causes a significant increase in their aggressiveness. This paper is aimed at studying-after a period of fighting deprivation-the involvement of genes (associated with neurotransmitter systems within the nucleus accumbens) in the above phenomena. The nucleus accumbens is known to participate in reward-related mechanisms of aggression. We found the following differentially expressed genes (DEGs), whose expression significantly differed from that in controls and/or mice with positive fighting experience in daily agonistic interactions followed by fighting deprivation: catecholaminergic genes <i>Th</i>, <i>Drd1</i>, <i>Drd2</i>, <i>Adra2c</i>, <i>Ppp1r1b</i>, and <i>Maoa</i>; serotonergic genes <i>Maoa</i>, <i>Htr1a</i>, <i>Htr1f</i>, and <i>Htr3a</i>; opioidergic genes <i>Oprk1</i>, <i>Pdyn</i>, and <i>Penk</i>; and glutamatergic genes <i>Grid1</i>, <i>Grik4</i>, <i>Grik5</i>, <i>Grin3a</i>, <i>Grm2</i>, <i>Grm5</i>, <i>Grm7</i>, and <i>Gad1</i>. The expression of DEGs encoding proteins of the GABAergic system in experienced aggressive male mice mostly returned to control levels after fighting deprivation, except for <i>Gabra5</i>. In light of the conceptual paradigm for analyzing data that was chosen in our study, the aforementioned DEGs associated with the behavioral pathology can be considered responsible for consequences of aggression followed by fighting deprivation, including mechanisms of an aggression relapse.