Seite - (000177) - in Biomedical Chemistry: Current Trends and Developments

individuals). A common example is the prescription of methylphenidate, a DAT blocker, to attention-deficit hyperactivity disorder (ADHD) patients (Agay, 2010; Gamo, 2010). Likewise, most typical and atypical antipsychotic drugs display a significant affinity to dopaminergic (and serotonergic) receptors. Deficient decision-making, judgment capacity and impulse control are likely to result in increased risk-tanking and facilitate drug experimentation, binge intoxication and development of addictive behaviors (either substance or non-substance dependent). Addiction to drugs refers to the loss of control over drug intake or the compulsivity to seek and consume drugs despite adverse effects. Addiction only occurs through repeated exposure and implies adaptations of several pathways at the molecular and cellular levels (Nestler, 2001). Behavioral adaptations in addiction result from the dysfunctional interaction of three key neural systems: an hyperactive/impulsive amygdala-striatum loop that promotes automatic and repetitive behaviors; an hypoactive/reflective PFC, impairing decision-making; and the insula-dependent decision-making processes related to uncertain risk/reward, which potentiates impulsivity and weakens the cognitive function (Evans, 2008; Noel, 2013). In addicted persons, the uncontrollable urge to obtain drugs and relapse is associated with a pathological balance between excitatory and inhibitory neurotransmission circuits, leading to persistent behavioral abnormalities (Winder, 2002). Changes in DA balance are also implicated in the physiopathology of other psychiatric conditions, such as schizophrenia, and anxiety and mood disorders (Willner, 2005; Chaudhury, 2013; Tye, 2013). In schizophrenia, manifestation of the positive symptoms (hallucinations, delusions and psychosis) is a consequence of an hiperactive mesolimbic DA system, while hipofrontality is linked to reduced mesocortical DA function (Abi-Dargham, 2002). Although it is now accepted that DA deregulation in schizofrenia is secondary to the GABAergic dysfuntion, most therapeutic approaches target the DA and 5-HT receptors. The role of DA in anxiety disorders has long been acknowledged. Within mood disorders, DA is strongly implicated in depression-bipolar states, where the mania/depression cycling was associated with hyper/hypodopaminergic states (Cousins, 2009).