Synthetic cathinones (also known as ¿bath salts¿) recently emerged as a novel class of psychoactive drug with documented abuse potential. In addition, prolonged cathinones abuse is associated with impaired mood, social interactions, and cognition in humans. Notably, synthetic cathinones are often detected in toxicological analysis of patients presenting at emergency rooms with agitation, confusion/cognitive impairment and aggressive behaviour. Behavioural disturbances produced by acute intake may last beyond 4 weeks. Consistently, passive administration of these compounds in laboratory animals have confirmed several behavioural alterations, including: reduced social recognition, impaired memory, and reduced vocalizations (a proxy of communication deficit/social isolation).
The occurrence of social behaviour disturbances with relation to cathinones use patterns has not been systematically investigated and, at present, is largely based on case reports. This frame is complicated by the presence in the drug market of a huge and ever-growing variety of molecules, designed to mimic illegal substances like cocaine, methamphetamine and MDMA. In this concerning scenario, it is imperative to predispose an animal model that accurately and fully reproduces features most pertinent to the abuse of cathinones.
Based on the above, the objective of this proposal is threefold: i) to study, in rats, the behaviour of self-administration under short- and long-term access conditions of two new synthetic cathinones, 4-MEC and alpha-PVP, with a different pharmacological profile; ii) to investigate the incubation of drug craving during abstinence and relapse into drug use and in parallel iii) to determine the time-course of social behaviour in rats trained to self-administer the drugs, as measured in the three-chambered social apparatus: specifically, the dynamics of social interactions in acute, chronic and during abstinence from drug use.
In the wide scenario of the so called 'Novel Psychoactive Substances', synthetic cathinones are considered one of the major classes based on scientific and governmental agencies reports. ER case reports and retrospectively analysed case-series form most of the current human literature on the topic, highlighting the health hazards and behavioural manifestations such as aggression and mood disorders. Unfortunately, no controlled studies have been performed, and detailed history of abuse patterns is missing. On the other hand, animal data have invariably confirmed the abuse potential of these compounds, and the impact on social preference. However, the animal models used (passive drug administration, or short-access self-administration) are not totally reliable, as they don't fully reproduce the many facets of the human condition. We intend to fill this gap by using a relevant animal model of drug addiction (Ahmed et al. 2012), that closely mimic aspects of human drug-use disorder like the loss of control over use, the escalation in dose, the 'incubation' of drug craving during abstinence. To the best of our knowledge, this is the first study addressing the development of social disturbances due to synthetic cathinones abuse. Given the clinical validity of the model, and the key role of social functioning in drug-use disorders, the data may help guide translational studies in the field.
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