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Front. Mol. Neurosci. | doi: 10.3389/fnmol.2018.00436

Broad and Region-Specific Impacts of the Synthetic Cannabinoid CP 55,940 in Adolescent and Adult Female Mouse Brains

 Emma Leishman1, Michelle N. Murphy1, Michelle I. Murphy1,  Kenneth Mackie1 and  Heather B. Bradshaw2*
  • 1Indiana University, United States
  • 2Indiana University Bloomington, United States

Relative to Δ9-tetrahydrocannabinol (THC), the synthetic cannabinoid CP 55,940 (CP) is significantly more potent and efficacious at cannabinoid receptors, the primary targets for endogenous cannabinoids (eCBs). eCBs belong to a large, interconnected lipidome of bioactive signaling molecules with a myriad of effects in optimal and pathological function. Recreational use of highly potent and efficacious synthetic cannabinoids is common amongst adolescents, potentially impacting brain development. Knowledge of the molecular outcomes of synthetic cannabinoid use will be important to develop more targeted therapies for synthetic cannabinoid intoxication and to prevent long-term disruption to the CNS. Here, we test the hypothesis that CP has age and region-dependent effects on the brain lipidome. Adolescent (post-natal day (PND) 35 and PND 50) and young adult female mice were given either an acute dose of CP or vehicle and brains were collected 2 hours later. 8 brain regions were dissected and levels of ~80 lipids were screened from each region using HPLC/MS/MS. CP had widespread effects on the brain lipidome in all age groups. Interestingly, more changes were observed in the PND 35 mice and more were reductions in a lipid’s concentration, including region-dependent lowering of eCB levels. CP levels were highest in the cortex at PND 35, the hippocampus at PND 50, and in the cerebellum in the adult. These data provide novel insights into how high-potency, synthetic cannabinoids drive different, age-dependent, cellular signaling effects in the brain.

Keywords: Synthetic cannabinoid, lipidomics, Endocannabinnoid, Prostagalandins, CNS, Lipoamine

Received: 17 Aug 2018; Accepted: 08 Nov 2018.

Edited by:

Ildikó Rácz, Universitätsklinikum Bonn, Germany

Reviewed by:

Valéria De Almeida, Universidade Estadual de Campinas, Brazil
Laura Bindila, Johannes Gutenberg University Mainz, Germany
Bruno Pradier, Brown University, United States  

Copyright: © 2018 Leishman, Murphy, Murphy, Mackie and Bradshaw. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Heather B. Bradshaw, Indiana University Bloomington, Bloomington, United States, hbbradsh@indiana.edu