Title: Dose‐ and Time‐Dependent Expression of Anxiety‐Like Behavior in the Elevated Plus‐Maze During Withdrawal From Acute and Repeated Intermittent Ethanol Intoxication in Rats
Abstract: Alcoholism: Clinical and Experimental ResearchVolume 31, Issue 11 p. 1811-1819 Dose- and Time-Dependent Expression of Anxiety-Like Behavior in the Elevated Plus-Maze During Withdrawal From Acute and Repeated Intermittent Ethanol Intoxication in Rats Zhongqi Zhang, Zhongqi Zhang From the Department of Anesthesiology, UC San Diego School of Medicine and VA San Diego Healthcare System, San Diego, California (ZZ, ACM, GS); and Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, California (ACM, GFK, GS).Search for more papers by this authorAndrew C. Morse, Andrew C. Morse From the Department of Anesthesiology, UC San Diego School of Medicine and VA San Diego Healthcare System, San Diego, California (ZZ, ACM, GS); and Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, California (ACM, GFK, GS).Search for more papers by this authorGeorge F. Koob, George F. Koob From the Department of Anesthesiology, UC San Diego School of Medicine and VA San Diego Healthcare System, San Diego, California (ZZ, ACM, GS); and Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, California (ACM, GFK, GS).Search for more papers by this authorGery Schulteis, Gery Schulteis From the Department of Anesthesiology, UC San Diego School of Medicine and VA San Diego Healthcare System, San Diego, California (ZZ, ACM, GS); and Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, California (ACM, GFK, GS).Search for more papers by this author Zhongqi Zhang, Zhongqi Zhang From the Department of Anesthesiology, UC San Diego School of Medicine and VA San Diego Healthcare System, San Diego, California (ZZ, ACM, GS); and Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, California (ACM, GFK, GS).Search for more papers by this authorAndrew C. Morse, Andrew C. Morse From the Department of Anesthesiology, UC San Diego School of Medicine and VA San Diego Healthcare System, San Diego, California (ZZ, ACM, GS); and Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, California (ACM, GFK, GS).Search for more papers by this authorGeorge F. Koob, George F. Koob From the Department of Anesthesiology, UC San Diego School of Medicine and VA San Diego Healthcare System, San Diego, California (ZZ, ACM, GS); and Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, California (ACM, GFK, GS).Search for more papers by this authorGery Schulteis, Gery Schulteis From the Department of Anesthesiology, UC San Diego School of Medicine and VA San Diego Healthcare System, San Diego, California (ZZ, ACM, GS); and Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, California (ACM, GFK, GS).Search for more papers by this author First published: 17 September 2007 https://doi.org/10.1111/j.1530-0277.2007.00483.xCitations: 48 Reprint requests: Gery Schulteis, PhD, Department of Anesthesiology, UC San Diego School of Medicine, and VA San Diego Healthcare System, 3350 La Jolla Village Drive, VAMC 125a, San Diego, CA 92161-5008; Fax: 858-822-5009; E-mail: [email protected] This work was supported by a VA Merit Award (GS), NIAAA Grants AA12800 (GS), AA08459 (GFK), and NIAAA Center Grant AA06420 (GFK). Andrew Morse was supported by NIAAA Training Grant T32-AA07456. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat Abstract Background: Withdrawal from acute bolus intraperitoneal (IP) injection of high doses of ethanol elicits anxiety-like behavior (e.g. Doremus et al., 2003; Gauvin et al., 1989, 1992) and conditioned place aversion (Morse et al., 2000). More recently we demonstrated that withdrawal from a single moderate dose of ethanol (2.0 g/kg) is accompanied by elevations in brain reward thresholds, and that repeated intermittent treatment with this dose results in a significant potentiation of reward deficit (Schulteis and Liu, 2006). Methods: In the current study, the time- and dose-dependent emergence of anxiety-like behavior was measured in the elevated plus-maze at various times (3 to 24 hours) after acute or 3 daily IP injections of ethanol (1.0, 2.0, or 3.0 g/kg). Rats receiving daily handling for 2 days, and a single anxiety opportunity to explore the maze on a third day were divided into 1 of several treatment protocols: (1) NAIVE conditions: vehicle IP on all 3 days; (2) ACUTE conditions: vehicle on the first 2 days, ethanol on the third day; or (3) REPEAT conditions: ethanol on all 3 days. Results: ACUTE ethanol elicited reduced exploration of the open arms of the elevated plus-maze in a dose- and time-dependent fashion: 1.0 g/kg failed to elicit any significant effects, whereas 2.0 and 3.0 g/kg ethanol elicited a significant anxiety-like response at 6 hours and 9 to 12 hours postinjection, respectively. REPEAT treatment was still without effect at any time point tested following 1.0 g/kg ethanol, but extended the time course of anxiety-like behavior after treatment with either 2.0 or 3.0 g/kg doses. REPEAT treatment with 2.0 and 3.0 g/kg ethanol also produced significant hypoactivity in the maze at some time points postinjection. Conclusions: Withdrawal from a single exposure to ethanol produces transient but significant anxiety-like behavior, and repeated intermittent bouts of intoxication result in a significant extension of the duration of effect. 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