The α2-adrenergic receptor agonist, clonidine, reduces alcohol drinking in alcohol-preferring (P) rats

Dennis D. Rasmussen, Laura Alexander, Julia Malone, David Federoff, Janice C. Froehlich

Research output: Contribution to journalArticle

13 Scopus citations


Evidence suggests that noradrenergic signaling may play a role in mediating alcohol-drinking behavior in both rodents and humans. We have investigated this possibility by administering clonidine to alcohol-drinking rats selectively bred for alcohol preference (P line). Clonidine is an α2-adrenergic receptor agonist which, at low doses, inhibits noradrenergic signaling by decreasing norepinephrine release from presynaptic noradrenergic neurons. Adult male P rats were given 24h access to food and water and scheduled access to a 15% (v/v) alcohol solution for 2h daily. Rats received intra-peritoneal (IP) injections with clonidine (0, 10, 20, 40, or 80μg/kg body weight [BW], 10-11 rats/treatment group) once/day at 30min prior to onset of the daily 2h alcohol access period for 2 consecutive days. Clonidine, in doses of 40 or 80μg/kg BW, significantly reduced alcohol intake on both days of treatment (p<0.001). Two weeks later, rats were treated with clonidine for 5 consecutive days and clonidine, in doses of 40 or 80μg/kg BW, reduced alcohol intake on all 5 treatment days (p<0.001). Clonidine did not alter water consumption during the daily 2h free-choice between alcohol and water. In a separate group of male P rats, clonidine (40μg/kg BW) suppressed intake of a saccharin solution (0.04g/L). These results are consistent with and complement our previous findings that the α1-adrenergic receptor antagonist, prazosin, decreases voluntary alcohol drinking in alcohol-preferring rats, but suggests that effects of clonidine may not be specific for alcohol. The results suggest that although activation of the noradrenergic system plays an important role in mediating voluntary alcohol drinking, care is needed in selecting which drugs to use to suppress central noradrenergic signaling in order to maximize the selectivity of the drugs for treating alcohol-use disorders.

Original languageEnglish (US)
Pages (from-to)543-549
Number of pages7
Issue number6
StatePublished - Sep 1 2014


  • Alcohol
  • Clonidine
  • Ethanol
  • Noradrenergic
  • Norepinephrine
  • P rat

ASJC Scopus subject areas

  • Biochemistry
  • Medicine(all)
  • Behavioral Neuroscience
  • Neurology
  • Toxicology
  • Health(social science)

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