Laura H Corbit1, Patricia H Janak. 1. Department of Neurology, Ernest Gallo Clinic and Research Center, University of California, San Francisco, California, USA. lcorbit@gallo.ucsf.edu
Abstract
BACKGROUND: Conditioned stimuli are thought to play an important role in maintaining ethanol use and inducing relapse. Therefore, understanding the mechanisms through which such stimuli trigger ethanol seeking is of interest in the study and treatment of alcoholism. METHODS: This series of experiments examined the impact of ethanol-associated cues on ethanol-seeking behavior using a Pavlovian-instrumental transfer design. Rats received Pavlovian training in which an auditory stimulus predicted ethanol (10%) delivery. In a separate instrumental training phase, animals were trained to press a lever for ethanol. In the test phase, the impact of the stimulus on instrumental performance was assessed in extinction by presenting the stimulus while animals were free to perform the lever-press response. Experiment 2 assessed the selectivity of the transfer effect; rats received training with 2 auditory stimuli which predicted either ethanol or sucrose (2%) delivery and were trained to perform 2 instrumental responses, one earning ethanol and the other earning sucrose. Finally, Experiment 3 examined the selectivity of PIT using 2 natural rewards (sucrose and polycose). RESULTS: The results from Experiment 1 show that ethanol supports excitatory conditioning and that ethanol-associated cues facilitate instrumental performance for ethanol. When the selectivity of the transfer effect was examined in Experiment 2, the ethanol-paired stimulus was found to have a general excitatory effect on reward-seeking behavior, affecting both ethanol-directed and sucrose-directed responding equally. In contrast, the sucrose-paired stimulus had a selective effect, elevating sucrose-directed responding only. Experiment 3 confirms that selective transfer is observed when 2 natural rewards are used to reinforce responding. CONCLUSIONS: These data provide further evidence that ethanol-associated cues can drive ethanol-seeking behaviors. Because ethanol-associated cues also enhanced seeking behavior for a nonalcohol reward, these results additionally suggest that the modulation of reward-directed behaviors by cues associated with ethanol versus natural rewards may rely on different behavioral and neural mechanisms.
BACKGROUND: Conditioned stimuli are thought to play an important role in maintaining ethanol use and inducing relapse. Therefore, understanding the mechanisms through which such stimuli trigger ethanol seeking is of interest in the study and treatment of alcoholism. METHODS: This series of experiments examined the impact of ethanol-associated cues on ethanol-seeking behavior using a Pavlovian-instrumental transfer design. Rats received Pavlovian training in which an auditory stimulus predicted ethanol (10%) delivery. In a separate instrumental training phase, animals were trained to press a lever for ethanol. In the test phase, the impact of the stimulus on instrumental performance was assessed in extinction by presenting the stimulus while animals were free to perform the lever-press response. Experiment 2 assessed the selectivity of the transfer effect; rats received training with 2 auditory stimuli which predicted either ethanol or sucrose (2%) delivery and were trained to perform 2 instrumental responses, one earning ethanol and the other earning sucrose. Finally, Experiment 3 examined the selectivity of PIT using 2 natural rewards (sucrose and polycose). RESULTS: The results from Experiment 1 show that ethanol supports excitatory conditioning and that ethanol-associated cues facilitate instrumental performance for ethanol. When the selectivity of the transfer effect was examined in Experiment 2, the ethanol-paired stimulus was found to have a general excitatory effect on reward-seeking behavior, affecting both ethanol-directed and sucrose-directed responding equally. In contrast, the sucrose-paired stimulus had a selective effect, elevating sucrose-directed responding only. Experiment 3 confirms that selective transfer is observed when 2 natural rewards are used to reinforce responding. CONCLUSIONS: These data provide further evidence that ethanol-associated cues can drive ethanol-seeking behaviors. Because ethanol-associated cues also enhanced seeking behavior for a nonalcohol reward, these results additionally suggest that the modulation of reward-directed behaviors by cues associated with ethanol versus natural rewards may rely on different behavioral and neural mechanisms.