A SINGLE BINGE OF N-ETHYLPENTHYLONE (NEP) AND 4-CHLOROETHCATHINONE (4-CEC) INDUCES IMMEDIATE AND DURABLE COGNITIVE IMPAIRMENT IN YOUNG MICE

Synthetic cathinones (SC), usually produce fast-acting but short-lived stimulant effects, which trigger higher desire of redosing and potential risk of overdosing. Its consumption occurs frequently in binge administration (frequent administration during a single exposure-event), mostly by young party attendees. Adolescence is considered a second period of brain development and any disruption has a high risk of leading to altered brain function. Currently, there is contradictory and limited information approaching the short-term, even fewer the long-term cognitive function implications arising from SC use during adolescence, and even scarcer through binge exposure. The aim of this study was to evaluate the cognitive effects of SC arising from binge exposure at younger ages. Hence, the short- and long-term effect on learning/memory ability of mice exposed to SC N-ethylpenthylone (NEP) and 4-chloroethcathinone (4-CEC) single-binge was evaluated by the Morris watermaze (WM) a test used to evaluate spatial learning/memory effects in rodents.

Young (1-month) and adult (6-months) mice were exposed to a single-binge (2x16mg/kg or 2x32mg/kg, 2h interval) of NEP, 4-CEC or saline and the induced learning/memory effects assessed in a WM setup starting 24h (short-) and 1-month (long-term) after exposure.

Results showed that NEP and 4-CEC 32 mg/kg single-binge induced significant gap in escape latency from D5 and D4 onwards, respectively, compared with controls in young mice, while with adults it happened from D3 onwards. Even when trained 1-month post-exposure a similar learning profile was observed but with additional delay in learning on d2 versus d1 training, for both ages, at 4-CEC 16 mg/kg. The memory score was also affected at short-/long-term for any tested dose except at long-term for those young mice administered 16 mg/kg NEP.

These results suggest a potential risk of sustained cognitive impairment from single-binge exposure to SC, hence its use may pose a considerable cognitive and mental health concern.

Acknowledgements: funds from FCT: PTDC/SAU-TOX/32515/2017 to Álvaro Lopes, and in part by UIDB/04138/2020 and UIDP/04138/2020 to iMed.ULisboa. Florindo acknowledges the FCT (PTDC/SAU-TOX/32515/2017) for his fellowships.