Review: The neuropathology of drug abuse

Abstract

Drug abuse represents a significant health issue. The major substances abused include cannabis, opiates, cocaine, amphetamine, methamphetamine and 'ecstasy'. Alterations of intracellular messenger pathways, transcription factors and immediate early genes within the brain reward system seem to be fundamentally important for the development of addiction and chronic drug abuse. Genetic risk factors and changes in gene expression associated with drug abuse are still poorly understood. Besides cardiovascular complications, psychiatric and neurologic symptoms are the most common manifestations of drug toxicity. A broad spectrum of changes affecting the central nervous system is seen in drug abusers. The major findings result from the consequences of ischaemia and cerebrovascular diseases. Except for a few observations of vasculitis, the aetiology of these cerebrovascular accidents is not fully understood. The abuse of amphetamine, methamphetamine and MDMA has been related to neurotoxicity in human long-term abusers and to the risk of developing Parkinson's disease. However, whether such neurotoxicity occurs remain to be established. Systematic histological, immunohistochemical and morphometric investigations have shown profound morphological alterations in the brains of polydrug abusers. The major findings comprise neuronal loss, neurodegenerative alterations, a reduction of glial fibrillary acidic protein-immunopositive astrocytes, widespread axonal damage with concomitant microglial activation as well as reactive and degenerative changes of the cerebral microvasculature. These observations demonstrate that drugs of abuse initiate a cascade of interacting toxic, vascular and hypoxic factors, which finally result in widespread disturbances within the complex network of central nervous system cell-to-cell interactions.

Altered social and non-social decision-making in recreational and dependent cocaine users

“…Cocaine is classified as a highly addictive drug (Nutt et al 2007) and it is estimated that 5-6% of users will meet dependence criteria within the first year of use and around 21% by the age of 45 years (Wagner & Anthony, 2007). The health risks associated with cocaine abuse include severe medical complications, such as cardiovascular or respiratory incidences, and a number of psychiatric disorders (Buttner, 2012). Because drug addiction results in high economic and societal costs (Olesen et al 2012), and effective pharmacological treatment options are currently lacking (O'Brien, 2005), an adequate characterization of the core feature of cocaine addiction, maladaptive decision-making, is crucial for the development of effective prevention and treatment strategies.…”

The pathway to substance misuse for young people with ADHD and conduct disorder

“…Imaging studies demonstrate atypical markers in pre-frontal regions, and in their pathways to the basal ganglia-which collectively are known to be involved in dopaminergic circuitry (Wise, 2002). Dopaminergic activity is linked to reward circuits, which have been found in experimental tasks to represent processes of substance abuse and dependence in the form of impaired and impulsive decision-making abilities (Butner, 2011;Koob & Volkow, 2010;Urcelay & Dalley, 2012). Substance dependency also decreases sensitivity for the effects of rewards and affects, motivation and cognitive-control , which may have implications for self-regulation.…”

Role of Multifunctional FADD (Fas-Associated Death Domain) Adaptor in Drug Addiction

“…norcocaine) can induce various forms of neurotoxicity (Büttner, 2011), including apoptotic effects in both cultured cells (Xiao et al, 2000;Cunha-Oliveira et al, 2008) and the developing brain (Novikova et al, 2005). However, the aberrant activation of several cell death mechanisms by cocaine, including those mediated by the Fas/FADD complex, in the adult rat brain remains inconclusive (Dietrich et al, 2005;García-Fuster et al, 2009).…”

“…Besides the role of FADD in the cascades of apoptotic signaling in drug addiction (García-Fuster et al, 2007a, 2008bRamos-Miguel et al, 2009;Álvaro-Bartolomé et al, 2011), several pathways have been postulated to link FADD with some forms of behavioral plasticity induced by drugs of abuse, especially heroin/morphine (Ramos-Miguel et al, 2009, 2011 and cocaine , 2011Álvaro-Bartolomé et al, 2011) (Fig. 3).…”

“…It is generally accepted that some addictive drugs can induce cell death in the human brain, following observations that neurons and astrocytes die when exposed to drugs of abuse (Cunha-Oliveira et al, 2008;Büttner, 2011). Neurotoxicity and neuroplasticity acting together in the addicted brain might explain the dampened cognition and the reinforced behaviors driving to drug consumption.…”