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Journal of Basic and Clinical Physiology and Pharmacology

Editor-in-Chief: Horowitz, Michal

Editorial Board: Das, Kusal K. / Epstein, Yoram / S. Gershon MD, Elliot / Kodesh , Einat / Kohen, Ron / Lichtstein, David / Maloyan, Alina / Mechoulam, Raphael / Roth, Joachim / Schneider, Suzanne / Shohami, Esther / Sohmer, Haim / Yoshikawa, Toshikazu / Tam, Joseph

CiteScore 2016: 1.01

SCImago Journal Rank (SJR) 2016: 0.349
Source Normalized Impact per Paper (SNIP) 2016: 0.495

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Volume 29, Issue 1


Seizure vulnerability and anxiety responses following chronic co-administration and acute withdrawal of caffeine and ethanol in a rat model

Daniel Matovu
  • Department of Pharmacology and Therapeutics, Faculty of Medicine, Mbarara University of Science and Technology, Mbarara, Uganda
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Paul E. Alele
  • Corresponding author
  • Department of Pharmacology and Therapeutics, Faculty of Medicine, Mbarara University of Science and Technology, Mbarara, Uganda, Phone: +256773775132, Fax: +256485420782
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2017-11-11 | DOI: https://doi.org/10.1515/jbcpp-2017-0018



Caffeine antagonizes the intoxicating effects of alcohol. Consequently, there has been a dramatic global increase in the consumption of caffeinated drinks together with alcohol, especially among young adults. We assessed the seizure vulnerability and anxiety responses following the chronic co-administration of, and withdrawal from, caffeine and ethanol in male rats.


The rats were randomly assigned to six groups consisting of 10 animals each: 10 mg/kg of caffeine, 20 mg/kg of caffeine, 4 g/kg of 20% ethanol, combined caffeine (20 mg/kg) and ethanol (4 g/kg of 20%), 4 mL/kg distilled water, and an untreated control group. The test substances were administered intragastrically twice daily for 29 days. On day 29, the rats were tested on the elevated plus maze to assess anxiety-related responses. On day 30, pentylenetetrazol (PTZ), a chemoconvulsant, was administered intraperitoneally at a dose of 40 mg/kg to the animals. Seizure responses and mortality up to 72 h were recorded.


Compared with the control group, the rats that received chronic treatment with low-dose caffeine, ethanol alone, and combined caffeine and ethanol exhibited significant anxiogenic-like effects, unlike with high-dose caffeine. Both low- and high-dose caffeine significantly increased PTZ seizure latency. Ethanol alone and combined caffeine and ethanol both lowered PTZ seizure latency. No significant difference occurred between the controls and the untreated group for either anxiety or seizure expression. Combined caffeine and ethanol increased the seizure-induced mortality from withdrawal effects at 72 h.


These findings suggest that the chronic co-administration of caffeine and ethanol and the acute withdrawal from these drugs lead to anxiogenic effects and increased seizure vulnerability.

Keywords: acute withdrawal; anxiety; caffeine; chronic; elevated plus maze; ethanol; pentylenetetrazol; seizures


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About the article

Received: 2017-02-18

Accepted: 2017-08-31

Published Online: 2017-11-11

Published in Print: 2018-01-26

Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

Research funding: None declared.

Employment or leadership: None declared.

Honorarium: None declared.

Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

Citation Information: Journal of Basic and Clinical Physiology and Pharmacology, Volume 29, Issue 1, Pages 1–10, ISSN (Online) 2191-0286, ISSN (Print) 0792-6855, DOI: https://doi.org/10.1515/jbcpp-2017-0018.

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