Innate cocaine-seeking vulnerability arising from loss of serotonin-mediated aversive effects of cocaine in rats.

Ying S Chao, Jeffrey Parrilla-Carrero, Maya Eid, Oliver P Culver, Tyler B Jackson, Rachel Lipat, Makoto Taniguchi, Thomas C Jhou

Cell reports 2023 May 30

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Cocaine blocks dopamine reuptake, thereby producing rewarding effects that are widely studied. However, cocaine also blocks serotonin uptake, which we show drives, in rats, individually variable aversive effects that depend on serotonin 2C receptors (5-HT2CRs) in the rostromedial tegmental nucleus (RMTg), a major GABAergic afferent to midbrain dopamine neurons. 5-HT2CRs produce depolarizing effects in RMTg neurons that are particularly strong in some rats, leading to aversive effects that reduce acquisition of and relapse to cocaine seeking. In contrast, 5-HT2CR signaling is largely lost after cocaine exposure in other rats, leading to reduced aversive effects and increased cocaine seeking. These results suggest a serotonergic biological marker of cocaine-seeking vulnerability that can be targeted to modulate drug seeking. Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.

Citation

Ying S Chao, Jeffrey Parrilla-Carrero, Maya Eid, Oliver P Culver, Tyler B Jackson, Rachel Lipat, Makoto Taniguchi, Thomas C Jhou. Innate cocaine-seeking vulnerability arising from loss of serotonin-mediated aversive effects of cocaine in rats. Cell reports. 2023 May 30;42(5):112404