ROLES OF CANNABINOID TYPE 1 RECEPTORS IN THE MICE PREFRONTAL CORTEX FOR OBJECT LOCATION MEMORY

Abstract Background The cannabinoid type 1 receptor (CB1R) is stimulated by delta 9-tetrahydrocannabinol (THC) is the main component of cannabis. CB1R is a seven transmembrane Gi/o protein-coupled receptor. CB1Rs are mainly expressed in the brain1,2. CB1R regulates the release of some neurotransmitters from neurons such as GABAergic neurons3.Therefore CB1R is involved in the cognitive function such as memory4. The prefrontal cortex (PFC) is the brain region related to cognitive function5. The PFC is reported to be important for spatial cognitive function5,6. Aims and Objectives The relationship between CB1Rs in the PFC and spatial cognitive function remains unclear. In this study, we attempted to investigate the role of CB1R in the PFC by using the object location memory test, which can measure spatial cognitive function. Methods In this study, we administered arachidonylcyclopropylamide (ACPA) (10 ng/mice), a CB1R agonist, into the PFC of C57BL/6J mice (9 weeks, male) with the guide cannula and performed object location test. In object location test, memory formation was divided into three phases; acquisition, consolidation, and retrieval. First, we administered ACPA in three points. Second, we administered ACPA in once at each phase. Results The three intra-PFC administration of ACPA impaired object location memory. Furthermore, the single intra- PFC administration of ACPA impaired the memory acquisition. However, the consolidation and retrieval were not impaired. Discussion and Conclusion In this study, it was indicated that CB1R in PFC is associated with the acquisition of object location memory. These results may be useful for the functional analysis of CB1R in the PFC. References 1.Herkenham M, Lynn AB, Johnson MR, Melvin LS, de Costa BR, Rice KC (1991), Characterization and localization of cannabinoid receptors in rat brain: A quantitative in vitro autoradiographic study. J Neurosci. 11:563-583. https://doi.org/10.1523/JNEUROSCI.11-02-00563.1991. 2.Grass M, Dragunow M, Faull RL (1997), Cannabinoid receptors in the human brain: a detailed anatomical and quantitative autoradiographic study in the fetal, neonatal and adult human brain. Neuroscience. 77:299-318. https://doi.org/10.1016/S0306-4522(96)00428-9. 3.Demuth DG, Molleman A (2006), Cannabinoid signalling. Life Sci. 78:549-563. https://doi.org/10.1016/j.lfs.2005.05.055. 4.Prini P, Zambeletti E, Manenti C, Gabaglio M, Parolaro D, Rubino T (2020) Neurobiological mechanisms underlying cannabis-induced memory impairment. Eur Neuropsychopharmacol. 36:181-190. https://doi.org/10.1016/j.euroneuro.2020.02.002. 5.Yan Z, Rein B (2020) Mechanisms of synaptic transmission dysregulation in the prefrontal. 27:445-465. https://doi.org/10.1038/s41380-021-01092-3. 6.Spellman T, Rigotti M, Ahmari SE, Fusi S, Gogos JA, Gordon JA (2015), Hippocampal-prefrontal input supports spatial encoding in working memory. Nature. 522:309-314. https://doi.org/10.1038/nature14445.