Role of Cannabinoid Receptor Type 2 in Acute Behavioral Responses to Graft Versus Host Disease in Male Mice.

Abstract

Introduction: Graft versus host disease (GVHD) is a debilitating consequence of bone marrow (BM) transplantation for the treatment of hematological cancers and other conditions. Previous studies have demonstrated that mouse models of GVHD result in significant prefrontal cortical (PFC) neuroinflammation, which is mitigated by global and microglial-selective deletion of the type 2 cannabinoid receptor (CB2R). This study examined whether genetic deletion of CB2R similarly rescues the acute behavioral dysregulation produced by GVHD.

Materials and methods: GVHD was initiated in C57BL/6 mice by irradiation followed by infusion of BM and splenocytes from major histocompatibility mismatched B10.BR donors. Fourteen-18 days after transplant, mice were exposed to a battery of behavioral tests.

Results: The primary behavioral effects of GVHD in wild-type mice were increased immobility in the open field and increased struggling in the forced swim. These effects of GVHD also occurred in global CB2R knockout mice and in mice with CB2R deletion in cells expressing CX3CR1, which includes microglia. GVHD did not affect social interactions, sucrose consumption, rotarod behavior, or time in the middle of the open field in any genotype.

Discussion: These data indicate that while CB2R deletion from the recipient mice protects against neuronal loss and inflammation in the brain, it does not protect against acute behavioral dysregulation.