Anxiety-like effects of meta-chlorophenylpiperazine in paradoxically sleep-deprived mice

Abstract

Chlorophenylpiperazines (CPP) are psychotropic drugs used in nightclub parties and are frequently used in a state of sleep deprivation, a condition which can potentiate the effects of psychoactive drugs. This study aimed to investigate the effects of sleep deprivation and sleep rebound (RB) on anxiety-like measures in mCPP-treated mice using the open field test. We first optimized our procedure by performing dose-effect curves and examining different pretreatment times in naïve male Swiss mice. Subsequently, a separate cohort of mice underwent paradoxical sleep deprivation (PSD) for 24 or 48h. In the last experiment, immediately after the 24h-PSD period, mice received an injection of saline or mCPP, but their general activity was quantified in the open field only after the RB period (24 or 48h). The dose of 5mgmL(-1) of mCPP was the most effective at decreasing rearing behavior, with peak effects 15min after injection. PSD decreased locomotion and rearing behaviors, thereby inhibiting a further impairment induced by mCPP. Plasma concentrations of mCPP were significantly higher in PSD 48h animals compared to the non-PSD control group. Twenty-four hours of RB combined with mCPP administration produced a slight reduction in locomotion. Our results show that mCPP was able to significantly change the behavior of naïve, PSD, and RB mice. When combined with sleep deprivation, there was a higher availability of drug in plasma levels. Taken together, our results suggest that sleep loss can enhance the behavioral effects of the potent psychoactive drug, mCPP, even after a period of rebound sleep.

Keywords: CPP; CTRL; Chlorophenylpiperazines; Control; Designer drugs; Intraperitoneal; LC-MS/MS; Liquid chromatography-tandem mass spectrometry; MDMA; MTBE; Meta-chlorophenylpiperazine; Methyl tert-butyl ether; Methylenedioxymethamphetamine; OF; Open field; Orto-chlorophenylpiperazine; PSD; Paradoxical sleep deprivation; QC; Quality control; RB; SRM; Selected reaction monitoring; Sleep deprivation; Sleep rebound; ip; mCPP; oCPP.