The Effect of Cues on Aversion-Resistant Drinking in Long-Evans Rats
Continued drug use despite negative consequences is a behavior commonly seen in those affected by substance use disorder (SUD). It has been hypothesized that continued drug use despite aversive consequences can be triggered by exposure to drug-related cues. In this study, male and female Long-Evans rats were trained to self-administer 15% ethanol in operant boxes following a period of homecage intermittent alcohol access. During self-administration training, half were exposed to a light-sound stimulus paired with ethanol administration after each active lever press, and the other half received ethanol with no paired stimulus. After at least twelve sessions under these conditions, quinine-adulterated ethanol was used instead of regular ethanol in order to serve as an aversive consequence model. We found that males consumed more ethanol than their female counterparts during homecage access, which is inconsistent with prior literature showing that females generally consume more g/kg ethanol. In the group trained with cues, only males decreased their active lever presses when ethanol was adulterated with quinine, consistent with prior literature demonstrating increased aversion resistance in female rodents. Additionally, while quinine-adulteration did not impact alcohol self-administration in no-cue rats, rats in this group required more training to reach self-administration criteria, only a subset of rats ever met criteria to be tested with quinine (2 males, 1 female), and baseline self-administration was lower prior to quinine adulteration. This limits our ability to draw strong conclusions regarding the impact of cues on aversion-resistance. Additional experiments examining self-administration in a larger sample size, with more reliable self-administration in the absence of cues, are necessary to assess the impact of cues on compulsive alcohol seeking. It is important to obtain a better understanding of how cues can influence relapse or compulsive drug use to better grasp both the neurological components of and ways to reduce or eliminate relapse events.