Allen Mia I, Lewis Emory, Rough Cameron F, Nader Michael A
Department of Translational Neuroscience, Wake Forest University School of Medicine, NRC 546, Medical Center Blvd, Winston-Salem, NC, 27157-1083, USA.
Center for Addiction Research, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
Psychopharmacology (Berl). 2025 Mar 30. doi: 10.1007/s00213-025-06780-4.
Although ethanol consumption is ubiquitous among individuals who use cocaine, most preclinical work investigating factors that contribute to the development of problematic cocaine use do not incorporate ethanol into their experimental designs. Given that only a subset of individuals who try cocaine go on to develop a cocaine use disorder (CUD) research is needed to identify factors, such as ethanol consumption, that may influence vulnerability to cocaine reinforcement.
Thus, this study aimed to determine how a history of ethanol self-administration and exposure immediately prior to the first experience with cocaine self-administration influenced the potency of cocaine to function as a reinforcer in socially housed male and female cynomolgus monkeys.
For these experiments, one group of monkeys (n = 7) was trained to self-administer up to 1.5 g/kg of ethanol prior to cocaine self-administration while another group of monkeys (n = 13) remained ethanol-naïve through the study. Acquisition of cocaine self-administration was studied in both groups of monkeys under a fixed-ratio schedule of reinforcement where ascending doses of cocaine were substituted for food pellets. Cocaine ED50 values from the ascending limb were examined statistically.
The results showed that subordinate monkeys that self-administered ethanol prior to cocaine self-administration required higher cocaine doses to function as a reinforcer compared with subordinate monkeys not exposed to ethanol.
One possible explanation for this finding is that ethanol, due to its acute anxiolytic effects, mitigated the effect of chronic stress in subordinate monkeys and thereby blunted the reinforcing effects of initial cocaine exposure. Future research is needed to examine whether variables such as environmental enrichment or treatment with clinically effective anxiolytics in chronically stressed individuals can modify the initiation and continued use of cocaine.
尽管在使用可卡因的个体中，乙醇消费很普遍，但大多数研究导致可卡因使用问题发展的因素的临床前研究并未将乙醇纳入其实验设计中。鉴于只有一部分尝试使用可卡因的个体最终会发展为可卡因使用障碍（CUD），因此需要开展研究来确定可能影响可卡因强化易感性的因素，例如乙醇消费。
因此，本研究旨在确定乙醇自我给药史以及在首次可卡因自我给药之前立即接触乙醇如何影响可卡因在群居雄性和雌性食蟹猴中作为强化剂的效力。
在这些实验中，一组猴子（n = 7）在进行可卡因自我给药之前被训练自我给药高达1.5 g/kg的乙醇，而另一组猴子（n = 13）在整个研究过程中未接触过乙醇。在两组猴子中，按照固定比例强化程序研究可卡因自我给药的习得情况，其中用递增剂量的可卡因替代食物颗粒。对上升阶段的可卡因ED50值进行统计学检验。
结果表明，与未接触乙醇的从属猴子相比，在进行可卡因自我给药之前自我给药乙醇的从属猴子需要更高剂量的可卡因才能起到强化作用。
这一发现的一种可能解释是，乙醇由于其急性抗焦虑作用，减轻了从属猴子的慢性应激影响，从而减弱了最初可卡因暴露的强化作用。需要进一步研究以检查环境富集或对长期受压个体使用临床有效的抗焦虑药物等变量是否可以改变可卡因的起始使用和持续使用情况。
