INTERACTIONS OF SOCIAL EXPERIENCE, ALCOHOL SENSITIVITY, AND THE SEROTONERGIC SYSTEM

Abstract

Social isolation has been shown to correlate with increased alcohol consumption in various animal species. In humans, a decreased sensitivity to acute alcohol is correlated with future alcohol dependence and addiction. A plausible explanation for this correlation is that alcohol sensitivity decreases after isolation; however, our understanding of the mechanistic interaction between social isolation and sensitivity to acute alcohol is still in its infancy. The serotonergic system is one promising candidate that could be involved in this interaction because of its wide range of behavioral and physiological effects, especially those related to social experiences. In my dissertation, I investigated the roles of the serotonergic (5-HT) system with three separate aims: In the first aim, I measured the effects of several 5-HT agents (neurotoxin, reuptake blocker, and receptor agonist/antagonists) in freely-behaving crayfish that were communally housed (COMs) or individually isolated (ISOs) prior to ethanol (EtOH) exposure. I found that 5-HT is important in regulating the social differences in EtOH sensitivity, and 5-HT2βPRO receptors emerged as candidates to produce this interaction between 5-HT and EtOH. My results from this aim suggest that these receptors are downregulated in isolated crayfish, leading to reduced behavioral EtOH sensitivity. The second aim employed single-cell neurophysiology and pharmacology in the lateral giant (LG) circuit of reduced ex vivo crayfish preparations to investigate the cellular-molecular mechanisms that underlie the interaction between 5-HT and specific EtOH receptor targets. I found that the LG neurons are stimulated by EtOH, and social differences in EtOH sensitivity between COMs and ISOs are paralleled at the level of these single neurons. Specifically, my results suggest that social isolation causes downregulation of 5-HT2βPRO receptors and 5-HT1αPRO receptors on the LG neurons and upregulation of these receptors subtypes in GABAergic neurons that send feed-forward inhibition onto the LG neurons. In my third aim, I developed a wearable, miniature, cyclic voltammetry device that is capable of detecting (injected) monoamine neurotransmitters (including 5-HT) in freely-behaving crayfish. With improved sensor sensitivity in the future, this will allow measurements of 5-HT release patterns in crayfish with different social histories, including during EtOH exposure. Together, the results from my dissertation will inform work in other model systems and improve our understanding of the interactions between social experience, the 5-HT system, and alcohol use.