Introduction :Ketamine analogues, including 2-fluorodeschloroketamine (2-FDCK), are increasingly emerging as new psychoactive substances. The purpose ofthe current study was to compare the pharmacological and behavioral effects of ketamine and ketamine analogue 2-FDCK in vitro and in vivotests. Methods:The extracellular field excitatory postsynaptic potentials (fEPSP) were measured by whole-cell recording in mouse hippocampal slices. The intra-cellular Ca2+levels were detected by Fura-2/Ca2+imaging system in HEK293 cells, expressed with different NMDAR subunits (NR1/NR2A,NR2B, or NR2C). The locomotor activity was performed in an open field. The novel object recognition test (NORT) was performed in a wooded behavioral test box (40*40*40 cm). Motor coordination was assessed by an automated rotarod device. All self-administration sessions were con-ducted in the operant chambers equipped with two retractable levers and a stimulus light above each lever [1]. Results: The data showed the blocking effects of 2-FDCK on NMDA receptor-mediated fEPSP in mouse hippocampal slices and calcium influx in HEK293cells expressing NR1/NR2B subunits with similar potency to ketamine. However, 2-FDCK had slightly lower inhibitory effects than ketamine on NMDA-fEPSP in cells expressing NR1/NR2A and NR1/NR2C subunits. In mouse behavioral tests, 2-FDCK and ketamine equally induced locomo-tor hyperactivity and memory dysfunction in NORT. 2-FDCK produced more severe motor incoordination than ketamine in mice via the rotarod test. A higher dose of 2-FDCK was required to induce reinstatement following extinction from ketamine self-administration in rats. Conclusions: These findings imply that 2-FDCK has pharmacological and behavioral effects comparable with ketamine despite their slight differences inpotency.
Date:
2023-06-27
Relation:
British Journal of Pharmacology. 2023 Jun 27;180(Suppl. 1):1005.
