Histamine Regulates Accumbens Microcircuits: An Arousing Finding for Addiction Research

Abstract

The concept of “reward” is evolutionarily central as it is critical to reinforce behaviors that improve the chances of survival and reproduction and avoid behaviors that reduce fitness. Feelings of reward drive organisms to engage in behaviors like the consumption of calorie-dense foods or the pursuit of sexual reproduction, and some of the most crucial brain circuitry driving this reward is relatively well understood. One key reward region is the nucleus accumbens (NAc), which integrates information delivered by glutamatergic inputs from the hippocampus (providing information on previous experiences and context), the prefrontal cortex (conveying the organism’s current plan and goals), and the amygdala (affording emotional salience and relevance). The integration of all this information in the NAc is controlled by neuromodulatory neurotransmitters, the most well-studied being dopamine delivered by projections from the ventral tegmental area. Dopamine drives increased function of D1-type NAc medium spiny neurons (MSNs) comprising the direct pathway and reinforcing behavior, while the same dopamine drives down activity of D2-type NAc MSNs comprising the indirect pathway that prevent reinforcement. In more recent years, the understanding of other neuromodulatory signals and their effects on NAc function and outputs has emerged as a key goal, and histamine actions in the NAc is primary among these signals. SEE CORRESPONDING ARTICLE ON PAGE 1041 SEE CORRESPONDING ARTICLE ON PAGE 1041 Accumbal Histamine Signaling Engages Discrete Interneuron MicrocircuitsBiological PsychiatryVol. 93Issue 11PreviewCentral histamine (HA) signaling modulates diverse cortical and subcortical circuits throughout the brain, including the nucleus accumbens (NAc). The NAc, a key striatal subregion directing reward-related behavior, expresses diverse HA receptor subtypes that elicit cellular and synaptic plasticity. However, the neuromodulatory capacity of HA within interneuron microcircuits in the NAc remains unknown. Full-Text PDF