1 Department of Neurosciences, Faculty of Medicine, Université de Montréal, Montréal, QC, H3C 3J7, Canada.
2 Department of Psychology, Concordia University, Montréal, QC, H3G 1M8, Canada.
3 Department of Psychology, Université de Montréal, Montréal, QC, H3C 3J7, Canada.
4 Department of Pharmacology and Physiology, Faculty of Medicine, Université de Montréal, C.P. 6128, Succursale Centre-Ville Montréal, Montréal, Québec, H3C 3J7, Canada.
5 Department of Pharmacology and Physiology, Faculty of Medicine, Université de Montréal, C.P. 6128, Succursale Centre-Ville Montréal, Montréal, Québec, H3C 3J7, Canada. anna.samaha@umontreal.ca.
6 Neural Signaling and Circuitry Research Group (SNC), Faculty of Medicine, Université de Montréal, Montréal, QC, H3C 3J7, Canada. anna.samaha@umontreal.ca.
7 Center for Interdisciplinary Research On the Brain and Learning (CIRCA), Université de Montréal, Montréal, QC, H3C 3J7, Canada. anna.samaha@umontreal.ca.
8 Center for Studies in Behavioral Neurobiology, Department of Psychology, Concordia University, Montréal, QC, H3G 1M8, Canada. anna.samaha@umontreal.ca.

Rationale: When people with drug addiction encounter cues associated with drug use, this can trigger cravings and relapse. These cues can include conditioned stimuli (CSs) signaling drug delivery and discriminative stimuli (DSs) signaling drug availability. Compared to CS effects, DS effects are less explored in preclinical studies on cue-induced relapse.

Objective: We compared CS and DS effects on reward seeking following abstinence from intermittent-access cocaine (or sucrose) self-administration.

Methods: During 15-20 intermittent-access sessions, rats self-administered i.v. cocaine or sucrose pellets paired with a light-tone CS. Cocaine/sucrose was available for 5-min (signalled by a light; DS+) and unavailable for 25 min (signalled by different lighting conditions; DS-), and this cycled for 4 h/session. Following abstinence, we measured cocaine/sucrose seeking under extinction triggered by CS and DS presentation, and instrumental responding reinforced by these cues.

Results: Across intermittent-access sessions, rats increased lever pressing for cocaine or sucrose during DS+ periods and decreased responding during DS- periods. On days 2 and 21 of abstinence, only presentation of the DS+ or DS+ and CS combined elicited increased cocaine/sucrose-seeking behaviour (i.e., increased active lever presses). Presenting the DS- alongside the DS+ suppressed the increased cocaine-seeking behaviour otherwise produced by the DS+ . Finally, on day 21 of abstinence, rats showed equivalent levels of lever pressing reinforced by the DS+ , CS and by the DS+ and CS combined, suggesting comparable conditioned reinforcing value.

Conclusions: After intermittent self-administration, cocaine-associated DSs and CSs acquire similar conditioned reinforcing properties, but DSs more effectively trigger increases in drug seeking.