Single Exposure to the Cathinones MDPV and α-PVP Alters Molecular Markers of Neuroplasticity in the Adult Mouse Brain

Abstract

Synthetic cathinones have gained popularity among young drug users and are widely used in the clandestine market. While the cathinone-induced behavioral profile has been extensively investigated, information on their neuroplastic effects is still rather fragmentary. Accordingly, we have exposed male mice to a single injection of MDPV and α-PVP and sacrificed the animals at different time points (i.e., 30 min, 2 h, and 24 h) to have a rapid readout of the effect of these psychostimulants on neuroplasticity in the frontal lobe and hippocampus, two reward-related brain regions. We found that a single, low dose of MDPV or α-PVP is sufficient to alter the expression of neuroplastic markers in the adult mouse brain. In particular, we found increased expression of the transcription factor Npas4, increased ratio between the vesicular GABA transporter and the vesicular glutamate transporter together with changes in the expression of the neurotrophin Bdnf, confirming the widespread impact of these cathinones on brain plasticity. To sum up, exposure to low dose of cathinones can impair cortical and hippocampal homeostasis, suggesting that abuse of these cathinones at much higher doses, as it occurs in humans, could have an even more profound impact on neuroplasticity.

The Designer Drug αPHP Affected Cell Proliferation and Triggered Deathly Mechanisms in Murine Neural Stem/Progenitor Cells

“…As a matter of fact, neurogenesis is the process of generation of newborn neurons from NPSCs, located in precise and limited areas, occurring during embryonic and early postnatal stages, but also persisting during the adult mammalian life [ 38 , 39 ], when it plays a fundamental role in guaranteeing neuronal plasticity. Indeed, the CNS is particularly vulnerable to NPS and perturbation of adult neurogenesis may result in several long-lasting, irreversible impairments, including neuroplasticity alteration [ 31 ]. Therefore, in the current study we employed NPSCs as a powerful in vitro model [ 39 , 40 ], derived from eight-week-old mice with the goal to mimic the human exposure during puberty, hence trying to translationally assume the potential outcomes of permanent CNS damage in young NPS consumers.…”

“…The pharmacological activity of pyrovalerone derivatives has been also investigated, revealing that αPHP was able to trigger a selective and potent inhibition of dopamine and norepinephrine reuptake, showing instead negligible effects on serotonin transporters and also lacking the ability to increase neurotransmitter release [ 4 , 17 , 25 , 30 , 31 ].…”