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Novel evidence for endocannabinoid-mediated enhancement of cocaine intake in response to stress

Neuropsychopharmacology volume 48, pages 1119–1120 (2023)Cite this article

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Cocaine use disorder (CUD), like all substance use disorders, are complex in their etiology, trajectory, and opportunities for recovery. Many individual differences in personality traits, sensitivity to reward, social and economic status, and environment can all contribute to risk for and severity of a CUD. In particular, both momentary instances of stress and a history of high levels of lifetime stress are known to worsen cocaine use related outcomes [1]. Importantly, studies of frequent cocaine users have found that exposure to acutely stressful events increases reported levels of craving preceding instances of cocaine use [2]. Thus, the immediate effects of stress may directly act on physiological systems that promote further cocaine use. Indeed, several neural signaling processes, including glucocorticoid and endocannabinoid systems, are activated in response to stress and have the potential to both positively and negatively impact reward systems [3]. In turn, these processes may lead individuals to seek cocaine to cope with negative outcomes, or to even experience a heightened rewarding effect from cocaine. To investigate these possibilities, researchers have developed animal models assessing the effects of acute stress on cocaine-seeking behaviors.

In the paper titled, “Role of mesolimbic cannabinoid receptor 1 in stress-driven increases in cocaine self-administration in male rats,” McReynolds and colleagues expand upon an animal model they have developed that uses repeated daily footshock stress exposure to escalate cocaine intake, and investigated the role of the endocannabinoid system in this stress-induced increase in cocaine self-administration [4]. The authors used a clever design where intermittent, uncontrollable footshock was administered during 5-min bins prior to 30-min periods of access to cocaine self-administration. In each daily session, the rats were exposed to 4 of these 35-min footshock/self-administration blocks run in succession. The authors found that the rats rapidly escalate their cocaine intake after initiation of footshock stress exposure relative to no-stress controls and that the increase is observed in every self-administration block across days. Next, the authors stopped exposing the rats to the stressor and found that the enhanced cocaine intake was maintained for at least 5 days after stress cessation, with no sign of a return to baseline behavior. Moreover, footshock-exposed rats exhibited increased cocaine-primed reinstatement at three different doses of cocaine. Thus, the authors found both acute stress-induced increases in cocaine intake and long-lasting effects on relapse-related behavior of prior stress exposure.

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References

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  1. Department of Psychiatry, Translational Neuroscience Program, University of Pittsburgh, Pittsburgh, PA, 15219, USA

    Mary M. Torregrossa

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  1. Mary M. Torregrossa
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Correspondence to Mary M. Torregrossa.

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Torregrossa, M.M. Novel evidence for endocannabinoid-mediated enhancement of cocaine intake in response to stress. Neuropsychopharmacol. 48, 1119–1120 (2023). https://doi.org/10.1038/s41386-023-01602-7

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