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Objectives: Monoacylglycerol lipase (MAGL) is a cytosolic serine hydrolase considered a potential novel drug target for the treatment of CNS disorders including epilepsy. Here we examined MAGL levels in a rat model of epilepsy., Methods: Autoradiography has been used to validate the binding properties of the MAGL radiotracer, [ 3 H]T-401, in the rat brain, and to explore spatial and temporal changes in binding levels in a model of temporal lobe epilepsy model using unilateral intra-hippocampal injections of kainic acid (KA) in rats., Results: Specific and saturable binding of [ 3 H]T-401 was detected in both cortical grey and subcortical white matter. Saturation experiments revealed a K D in the range between 15 nM and 17 nM, and full saturation was achieved at concentrations around 30 nM. The binding could be completely blocked with the cold ligand (K i 44.2 nM) and at higher affinity (K i 1.27 nM) with another structurally different MAGL inhibitor, ABD 1970. Bilateral reduction in [ 3 H]T-401 binding was observed in the cerebral cortex and the hippocampus few days after status epilepticus that further declined to a level of around 30% compared to the control. No change in binding was observed in either the hypothalamus nor the white matter at any time point. Direct comparison to [ 3 H]UCB-J binding to synaptic vesicle glycoprotein 2 A (SV2A), another protein localized in the pre-synapse, revealed that while binding to MAGL remained low in the chronic phase, SV2A was increased significantly in some cortical areas., Significance: These data show that MAGL is reduced in the cerebral cortex and hippocampus in a chronic epilepsy model and indicate that MAGL inhibitors may further reduce MAGL activity in the treatment resistant epilepsy patient., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest relevant for this article., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)