Drug addiction: from bench to bedside

Abstract

Drug addiction is responsible for millions of deaths per year around the world. Still, its management as a chronic disease is shadowed by misconceptions from the general public. Indeed, drug consumers are often labelled as “weak”, “immoral” or “depraved”. Consequently, drug addiction is often perceived as an individual problem and not societal. In technical terms, drug addiction is defined as a chronic, relapsing disease resulting from sustained effects of drugs on the brain. Through a better characterisation of the cerebral circuits involved, and the long-term modifications of the brain induced by addictive drugs administrations, first, we might be able to change the way the general public see the patient who is suffering from drug addiction, and second, we might be able to find new treatments to normalise the altered brain homeostasis. In this review, we synthetise the contribution of fundamental research to the understanding drug addiction and its contribution to potential novel therapeutics. Mostly based on drug-induced modifications of synaptic plasticity and epigenetic mechanisms (and their behavioural correlates) and after demonstration of their reversibility, we tried to highlight promising therapeutics. We also underline the specific temporal dynamics and psychosocial aspects of this complex psychiatric disease adding parameters to be considered in clinical trials and paving the way to test new therapeutic venues.

Legalitas Penjualan Obat Psikotropika Secara Online Di Indonesia

“…psikotropika dapat mengakibatkan sindroma ketergantungan apabila penggunaannya tidak di bawah pengawasan dan petunjuk tenaga kesehatan yang mempunyai keahlian dan kewenangan untuk itu (Branch, 2011;Cheron, & d'Exaerde, 2021;Ifeoma et al, 2020). Penyalahgunaan juga memiliki dampak sosial, ekonomi, dan keamanan nasional, sehingga dikatakan sebagai ancaman bagi kehidupan bangsa dan negara (Glei, & Weinstein, 2019;Nyameh et al, 2013).…”

What Have We Learned (or Expect to) From Analysis of Murine Genetic Models Related to Substance Use Disorders?

“…The effect of DOA on long-term potentiation (LTP) and long-term depression (LTD) has been well-studied in VTA dopaminergic neurons (104)(105)(106). For instance, cocaine exposure increases the AMPA/NMDA receptor ratio, alters GluA2-containing AMPARs, and decreases NMDA receptor functionality in VTA dopaminergic neurons (107)(108)(109). Structural plasticity, which is the formation of new synaptic boutons and dendritic spines, is also observed after DOA exposure (110).…”

Striatonigrostriatal Spirals in Addiction

“…Dopamine projections come mainly from the VTA and SN (Beaulieu et al, 2014; Baik, 2020). The mesolimbic dopamine pathway is made up of dopaminergic projections from the VTA to the NAc (Cheron and Kerchove d'Exaerde, 2021). This midbrain to striatal pathway is a centerpiece to drugs of abuse, with virtually every abused drug stimulating dopaminergic transmission from the VTA to the NAc (Chiara and Imperato, 1988;Pontieri et al, 1996;Tanda et al, 1997).…”