QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, September 22, 2004, 24(38):8245-8252; doi:10.1523/JNEUROSCI.2179-04.2004

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (10) Citing Articles via Google Scholar Google Scholar Articles by López-Moreno, J. A. Articles by Navarro, M. Search for Related Content PubMed PubMed Citation Articles by López-Moreno, J. A. Articles by Navarro, M.

 Previous Article  |  Next Article 

Behavioral/Systems/Cognitive
Long-Lasting Increase of Alcohol Relapse by the Cannabinoid Receptor Agonist WIN 55,212-2 during Alcohol Deprivation

José Antonio López-Moreno,¹ Gustavo González-Cuevas,¹ Fernando Rodríguez de Fonseca,² and Miguel Navarro¹

¹Departamento de Psicobiología, Facultad de Psicología, Universidad Complutense de Madrid, E-28223 Madrid, Spain, and ²Unidad de Investigación, Fundación Hospital Carlos Haya, 29010 Málaga, Spain

Alcoholism is characterized by successive relapses. Recent data have shown a cross-talk between the cannabinoid system and ethanol. In this study, male Wistar rats with a limited (30 min sessions), intermittent, and extended background of alcohol operant self-administration were used. The relapse to alcohol after 1 week of alcohol deprivation was evaluated. Two weeks later, the animals were treated with the cannabinoid agonist WIN 55,212-2 (R-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1-naphthalenylmethanone mesylate) (0, 0.4, 2.0, and 10.0 mg/kg, s.c.) during a similar alcohol deprivation period, and alcohol relapse during 2 weeks was assessed. A conditioned place preference (CPP) paradigm was used to study the rewarding properties of the cannabinoid agonist. Locomotor activity was also recorded. All doses of WIN 55,212-2 produced aversion in the CPP paradigm. The doses of 2.0 and 10.0 mg/kg resulted in an important suppression of spontaneous locomotor activity and a progressive weight loss during the next 2 weeks. The single alcohol deprivation was followed by a transient increase in their responding for alcohol from a range of 20-24 lever presses at baseline to a range of 38-48 responses in the first and second days (alcohol deprivation effect). However, the administration of WIN 55,212-2 during ethanol deprivation produced similar increased responses for alcohol but in a long-term way (at least over 2 weeks). These findings suggest that noncontingent chronic exposure to cannabinoids during alcohol deprivation can potentiate the relapse into alcohol use, indicating that functional changes in the cannabinoid brain receptor may play a key role in ethanol relapse.

Key words: cannabinoid; WIN 55,212-2; ethanol operant self-administration; alcohol deprivation; relapse; craving

---

Received April 1, 2004; revised July 19, 2004; accepted July 21, 2004.

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help