Laura H Corbit1, Hong Nie, Patricia H Janak. 1. Ernest Gallo Clinic and Research Center, University of California at San Francisco, San Francisco, California, USA. laura.corbit@sydney.edu.au
Abstract
BACKGROUND: Addictions are defined by a loss of flexible control over behavior. The development of response habits might reflect early changes in behavioral control. The following experiments examined the flexibility of alcohol-seeking after different durations of self-administration training and tested the role of the dorsal striatum in the control of flexible and habitual alcohol self-administration. METHODS: Rats were trained to lever-press to earn unsweetened ethanol (EtOH) (10%). The sensitivity of the lever-press response to devaluation was assessed by prefeeding the rats either EtOH or sucrose before an extinction test after different amounts of training (1, 2, 4, and 8 weeks). We subsequently tested the role of the dorsomedial striatum (DMS) and dorsolateral striatum (DLS) in controlling alcohol seeking with reversible inactivation techniques (baclofen/muscimol: 1.0/.1 mmol/L, .3 μL/side). RESULTS: We find that operant responding for EtOH early in training is goal-directed and reduced by devaluation, but after 8 weeks of daily operant training, control has shifted to a habit-based system no longer sensitive to devaluation. Furthermore, after relatively limited training, when responding is sensitive to devaluation, inactivation of the DMS greatly attenuates the alcohol-seeking response, whereas inactivation of the DLS is without effect. In contrast, responding that is insensitive to devaluation after 8 weeks of training becomes sensitive to devaluation after inactivation of the DLS but is unaffected by inactivation of the DMS. CONCLUSIONS: These experiments demonstrate that extended alcohol self-administration produces habit-like responding and that response control shifts from the DMS to the DLS across the course of training.
BACKGROUND: Addictions are defined by a loss of flexible control over behavior. The development of response habits might reflect early changes in behavioral control. The following experiments examined the flexibility of alcohol-seeking after different durations of self-administration training and tested the role of the dorsal striatum in the control of flexible and habitual alcohol self-administration. METHODS:Rats were trained to lever-press to earn unsweetened ethanol (EtOH) (10%). The sensitivity of the lever-press response to devaluation was assessed by prefeeding the rats either EtOH or sucrose before an extinction test after different amounts of training (1, 2, 4, and 8 weeks). We subsequently tested the role of the dorsomedial striatum (DMS) and dorsolateral striatum (DLS) in controlling alcohol seeking with reversible inactivation techniques (baclofen/muscimol: 1.0/.1 mmol/L, .3 μL/side). RESULTS: We find that operant responding for EtOH early in training is goal-directed and reduced by devaluation, but after 8 weeks of daily operant training, control has shifted to a habit-based system no longer sensitive to devaluation. Furthermore, after relatively limited training, when responding is sensitive to devaluation, inactivation of the DMS greatly attenuates the alcohol-seeking response, whereas inactivation of the DLS is without effect. In contrast, responding that is insensitive to devaluation after 8 weeks of training becomes sensitive to devaluation after inactivation of the DLS but is unaffected by inactivation of the DMS. CONCLUSIONS: These experiments demonstrate that extended alcohol self-administration produces habit-like responding and that response control shifts from the DMS to the DLS across the course of training.
Authors: Herman H Samson; Christopher L Cunningham; Cristine L Czachowski; Ann Chappell; Brooke Legg; Erin Shannon Journal: Alcohol Date: 2004-04 Impact factor: 2.405
Authors: Rafael Renteria; Christian Cazares; Emily T Baltz; Drew C Schreiner; Ege A Yalcinbas; Thomas Steinkellner; Thomas S Hnasko; Christina M Gremel Journal: Elife Date: 2021-03-17 Impact factor: 8.140
Authors: Eric A Thrailkill; Sydney Trask; Pedro Vidal; José A Alcalá; Mark E Bouton Journal: J Exp Psychol Anim Learn Cogn Date: 2018-10 Impact factor: 2.478
Authors: Xuan Li; Maria B Carreria; Kailyn R Witonsky; Tamara Zeric; Olivia M Lofaro; Jennifer M Bossert; Jianjun Zhang; Felicia Surjono; Christopher T Richie; Brandon K Harvey; Hyeon Son; Christopher W Cowan; Eric J Nestler; Yavin Shaham Journal: Biol Psychiatry Date: 2017-12-29 Impact factor: 13.382