CD5 knockout modulates effects of alcohol consumption in mouse models (P1-12.008)

Abstract

<h3>Objective:</h3> We seek to elucidate the impact of cluster of differentiation 5 (CD5) expression on the effects of acute ethanol (EtOH) exposure. <h3>Background:</h3> CD5 is a transmembrane glycoprotein expressed on the surface of T and B1 cells. It has been previously shown that CD5 expression is altered by chronic EtOH consumption. Additionally, GABA neurons in the ventral tegmental area (VTA) are inhibited by EtOH, while dopamine neurons are excited. Given that some CD5+ lymphocytes may be involved in the regulation of inhibitory GABA synapses, we hypothesize that CD5 knockout may modulate the behavioral and physiological effects of EtOH consumption. <h3>Design/Methods:</h3> CD5 knockout (CD5KO) mice were compared to C57BL/6J wild type (WT) mice. CD5KO was confirmed with flow cytometry. Behavioral changes were measured via open field behavior, loss of righting reflex, and 24-hour access two bottle choice drinking. Neuronal dynamics were assessed using single-unit recordings, loose patch clamp recordings, fast scan cyclic voltammetry, and qRTPCR. <h3>Results:</h3> CD5KO mice displayed reduced EtOH consumption versus WT mice in two bottle choice drinking as well as decreased reduction in locomotor activity at low dose (0.5–2.0g/Kg) EtOH and decreased sedation at high dose (4.0g/Kg). Paired-pulse frequency response measure of dopamine release also differed between CD5KO and WT strains. Additionally, decreased levels of dopamine transporter (DAT) RNA were found in the nucleus accumbens. <h3>Conclusions:</h3> CD5KO mice may be less sensitive to some of the effects of EtOH, suggesting that CD5 may play a role in EtOH consumption and sedation. <b>Disclosure:</b> Mr. Amendolara has nothing to disclose. Dr. Payne has nothing to disclose. Dr. Obray has nothing to disclose. Mr. Williams has nothing to disclose. Ms. Small has nothing to disclose. The institution of Dr. Yorgason has received research support from American Osteopathic Association. Dr. Edwards has nothing to disclose. Dr. Weber has nothing to disclose. Dr. Steffensen has stock in Syzygy Innovations, LLC. Dr. Steffensen has received intellectual property interests from a discovery or technology relating to health care.