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Tianeptine Co‐administration with Alcohol to Adolescent Rats Modifies the Alcohol Withdrawal Syndrome
Author(s) -
Rhoads Dennis E.,
Martin Bryan,
Mauterer Madelyn,
Orlando Krystal
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.704.6
Subject(s) - tianeptine , alcohol , hypoactivity , alcohol withdrawal syndrome , medicine , self administration , ampa receptor , glutamate receptor , psychology , endocrinology , receptor , hippocampus , chemistry , biochemistry , antidepressant
Adolescence is a time when many individuals have their first experiences with alcohol and other drugs. It is a time when the brain undergoes important developmental changes that may be altered by drug use. We have shown previously that adolescent Long‐Evans rats consume high levels of an alcohol‐containing liquid diet, achieve correspondingly high blood alcohol concentrations, and develop a subsequent severe alcohol withdrawal syndrome. Using adult rats, tianeptine has been shown by other groups to decrease anxiety‐like behaviors and the onset and severity of convulsions during alcohol withdrawal. The present study was designed to test the effectiveness of tianeptine against the severe alcohol withdrawal syndrome seen with adolescent rats and to test the effects of tianeptine on upregulation of glutamate receptors during adolescent alcohol consumption. Liquid diets were used to administer alcohol and tianeptine, alone and in combination, using a modified chronic intermittent design. After 10 days of co‐administration of tianeptine and alcohol and 6 hours of withdrawal, motor activity showed little or none of the hypoactivity characteristic of alcohol withdrawal. Tianeptine alone had no effect on motor activity under these conditions. However, continued out to 21 days of co‐administration, adolescent rats showed the same high frequency of induced running episodes and convulsions during withdrawal as when alcohol was administered alone. Western blotting was used to determine expression levels for forebrain glutamate receptors, AMPA and NMDA. Both receptors were upregulated during chronic alcohol consumption. During co‐administration with alcohol, tianeptine delayed this upregulation so that at 10 days there was no significant upregulation of AMPA or NMDA whereas significant increases in expression were observed by 21 days. These results indicate that tianeptine may dampen symptoms of adolescent alcohol withdrawal in the short term by delaying the upregulation of excitatory glutamate receptors induced by chronic alcohol. However, tianeptine was ineffective in maintaining this delay and in preventing more severe withdrawal associated with longer term alcohol consumption. Thus, we conclude that tianeptine may be of limited effectiveness against alcohol withdrawal severity in adolescents compared to that suggested previously for adult rats. Support or Funding Information This work was supported by the Biology Department and School of Science of Monmouth University.