Abstract
The co-abuse of marijuana with cocaine is widespread, but it has not been until recently that the relationship between the behavioral effects of cannabinoids and cocaine has begun to be unveiled in animal models. Male Wistar rats were trained to intravenously self-administer cocaine until a stable baseline was reached. Rats then were subjected to a 5-day cocaine deprivation period during which they were treated daily with the cannabinoid receptor 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, 0.3, 1, and 3 mg/kg; i.p.). Following this subchronic treatment, rats were tested, in counterbalanced order, in a test of anxiety (elevated plus-maze), as well as extinction and cue-induced reinstatement tests, the latter conducted according to a between-within procedure. Subchronic administration of WIN 55,212-2 was found to produce dose-dependent alterations of performance in the extinction, reinstatement, and anxiety tests with the lowest dose of WIN 55,212-2 producing the highest resistance to extinction and reinstatement, and the highest dose of WIN 55,212-2 producing the highest anxiolytic activity. Subchronic treatment with WIN 55,212-2 in rats without a history of cocaine self-administration did not affect anxiety levels. The results suggest an important role of the cannabinoid system in neuronal processes underlying cocaine seeking behavior. However, further studies will be necessary to understand possible implications of these findings for a role of the cannabinoid system as a treatment target for human cocaine abuse.
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Acknowledgements
This work was supported by NIH/NIDA grant DA 07348 (FW) and by the Spanish Fondo de Investigación Sanitaria (Red de Trastornos Adictivos G03/05), the Comunidad Autónoma de Madrid GR/SAL/0541/2004, the Plan Nacional Sobre Drogas (Ministerio de Sanidad), The European Fifth Framework Programme QLRT-2000–01691 and the MEC SAF2005–04926, (MN). Gustavo González-Cuevas is a predoctoral fellow of the Ministerio de Educación y Cultura in Spain.
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González-Cuevas, G., Aujla, H., Martin-Fardon, R. et al. Subchronic Cannabinoid Agonist (WIN 55,212-2) Treatment during Cocaine Abstinence Alters Subsequent Cocaine Seeking Behavior. Neuropsychopharmacol 32, 2260–2266 (2007). https://doi.org/10.1038/sj.npp.1301365
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DOI: https://doi.org/10.1038/sj.npp.1301365
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