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Chronic Cannabinoid Administration to Periadolescent Rats Modulates the Metabolic Response to Acute Cocaine in the Adult Brain



To analyze brain metabolic response to acute cocaine in male and female Wistar rats with or without a history of cannabinoid exposure during periadolescence.


The synthetic cannabinoid agonist CP 55,940 (CP) or its vehicle (VH), were administered to male and female rats during periadolescence. When these animals reached adulthood, saline and cocaine-induced changes in 2-deoxy-2-[18F]fluoro-D-glucose (FDG) uptake were studied by positron emission tomography.


The baseline (post-saline) metabolism in the septal nuclei was higher in CP-females than in VH-females, although septal metabolism was lower in CP-females after cocaine, reaching similar values to those of VH-females at baseline. Cocaine did not affect metabolism in VH-females. Periadolescent cannabinoid treatment did not influence baseline metabolism in males although cocaine reduced the FDG uptake in the dorsal striatum of males that received the VH but not CP.


These results suggest that cannabinoids during periadolescence modify baseline and cocaine-evoked brain metabolism in a sex-dependent manner. In the case of CP-females, the involvement of septal metabolic alterations in their susceptibility to the rewarding effects of cocaine should be further investigated.

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The authors thank Alberto Marcos, Rosa Ferrado, and Luis Troca for their technical assistance and Dr. Mark Sefton for editorial assistance. The authors declare that they are entirely responsible for the scientific content of this paper. This work was supported by grants from the Ministerio de Educación y Ciencia (Grants nº SAF2004-08148 and SAF2007-064890); Ministerio de Sanidad y Consumo (Grants RD06/00170029 of Instituto de Salud Carlos III, PNSD 2004–2007 and 2008–2010); Dirección General de Investigación de la Comunidad de Madrid (Grant S-SAL/0261/2006, I+D CANNAB-CM Consortium); and UNED (Plan de Promoción de la Investigación) to EA, and grants from the “Ministerio de Ciencia y Tecnología” (TEC2004-07052-C02-01/TCM), “Ministerio de Sanidad y Consumo” (CIBER CB06/01/0079, PNSD 2007–2010, FIS CP08/00017), “Ministerio de Industria” (CENIT program) and “Fundación de Investigación Médica Mutua Madrileña” (2007–2010 and 2008–2011) to MD.

Conflict of Interest

The authors declare that they have no conflict of interest.

Author information

Correspondence to Alejandro Higuera-Matas.

Additional information

Significance: In the present report, we present combined PET/MR imaging evidence suggesting that periadolescent cannabinoid treatment to rats modifies the metabolic response to cocaine in adulthood in a sex-dependent manner. We also show for the first time in the rat that cocaine is associated with decreased metabolism in the dorsal striatum. This work extends previous findings by showing how the brain metabolic changes induced by cocaine are modulated by a chronic cannabinoid treatment.

An erratum to this article is available at

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Higuera-Matas, A., Soto-Montenegro, M.L., Montoya, G.L. et al. Chronic Cannabinoid Administration to Periadolescent Rats Modulates the Metabolic Response to Acute Cocaine in the Adult Brain. Mol Imaging Biol 13, 411–415 (2011).

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Key words

  • Cannabinoids
  • Cocaine
  • Dorsal striatum
  • PET
  • Septal nuclei