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Journal of Psychopharmacology
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Spontaneous cannabinoid withdrawal produces a differential time-related responsiveness in cannabinoid CB1 receptor gene expression in the mouse brain

José M. Oliva

Servicio de Psiquiatría y Unidad de Investigación, Hospital Universitario 12 de Octubre, Madrid, Spain.

Sergio Ortiz

Servicio de Psiquiatría y Unidad de Investigación, Hospital Universitario 12 de Octubre, Madrid, Spain.

Tomás Palomo

Servicio de Psiquiatría y Unidad de Investigación, Hospital Universitario 12 de Octubre, Madrid, Spain.

Jorge Manzanares

Servicio de Psiquiatría y Unidad de Investigación, Hospital Universitario 12 de Octubre, Madrid, Spain. jmanzanares6{at}terra.es

This study aimed to examine the behavioural and neurochemical (cannabinoid CB1 receptor gene expression) changes induced by spontaneous cannabinoid withdrawal in mice. Tolerance was assessed by measuring rectal temperature and motor activity in the open-field test after CP-55, 940 administration. Cannabinoid withdrawal symptoms were determined by measuring motor activity and behavioural signs of abstinence. Cessation of CP-55, 940 treatment in tolerant mice induced a spontaneous time-dependent behavioural withdrawal syndrome consisting of marked increases (140%) in motor activity, number of rearings (170%), decreases in grooming (57%), wet dog shakes (73%) and rubbing behaviours (74%) on day 1, progressively reaching values similar to vehicle-treated mice on day 3. Interestingly, this spontaneous cannabinoid withdrawal resulted in CB1 gene expression upregulation (20–30%) in caudate-putamen, ventromedial hypothalamic nucleus, central amygdaloid nucleus and CA1, whereas in the CA3 field of hippocampus, a significant decrease (15–20%) was detected. Taken together, the results of this study suggest that cessation of CP-55, 940 administration in tolerant mice produces a behavioural cannabinoid withdrawal syndrome and a selective and differential responsiveness in CB1 receptor gene expression in several brain regions of the mice. These findings further suggest a time and regional differential role for cannabinoid receptors in short- and long-term neuroadaptations that occur after exposure to cannabis derivatives.

Key Words: cannabinoids • gene expression • mRNA • withdrawal

Journal of Psychopharmacology, Vol. 18, No. 1, 59-65 (2004)
DOI: 10.1177/0269881104040238
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