Resumen de Neurochemical and psychopharmacological study of mdpv, a cocaine-like psychostimulant. Characterization of structurally-related second-generation synthetic cathinones
ABSTRACT Drugs of abuse represent a global problem not only at a health level, but also at a social and economic extent. Recently, a tidal wave of new emerging psychoactive substances has completely modified the illicit drug market, thereby hundreds of new drugs are being consumed by millions of people worldwide regardless most of these substances are hardly known. Among them, a new family of amphetamine derivatives named synthetic cathinones has surfaced, being 3,4-methylenedioxypyrovalerone (MDPV) one of the most popular members of the first-generation of these drugs. MDPV shares mechanism of action with cocaine and its consumption is often linked to severe acute intoxications, drug dependence and even deaths. In this context, this doctoral dissertation aims to contribute to scientific knowledge by providing new insights about MDPV, more concretely, about the neuroadaptive changes underlying its abuse, its addictive properties, its behavioural effects, as well as about its relationship with cocaine, the most consumed psychostimulant worldwide.
In summary, repeated exposure to MDPV induces behavioural abnormalities such as anxiety-related and risk-taking behaviours, aggressiveness and locomotor sensitization. Moreover, it exerts powerful rewarding effects. Importantly, a cross-sensitization and cross-reinstatement between MDPV and cocaine has been evidenced. Nonetheless, despite the great similarities between these two psychostimulants, the intracellular responses that they trigger in reward-related brain areas notably differ.
Whereas the first part of the present doctoral dissertation has been focused on studying MDPV, the second one has been devoted to characterizing the in vitro pharmacology as well as the psychostimulant and rewarding properties of structurally related new second-generation synthetic cathinones.
To sum up, all the compounds tested proved to be potent dopamine and noradrenaline uptake inhibitors, and their potency at inhibiting such transporters varies according to their amino terminal group. Furthermore, all of them exerted psychostimulant and rewarding effects in mice, a fact that evidences their abuse liability.
