However, a recent PET imaging study provides evidence that the initial action of SSRIs is an acute reduction in serotonin levels in terminal fields,105 in line with preclinical studies which have shown that the initial effect of SSRIs is to reduce firing in the raphe nucleus and serotonin levels in the terminal fields.107-113 In preclinical studies this acute effect resolves over the next few weeks of treatment as the raphe Inhibitors,research,lifescience,medical desensitizes.113 Thus, the reduction

in serotonin in terminal regions seen with acute citalopram in the human study could explain why SSRIs take some days to work, even worsening some symptoms initially. Non-monoaminergic targets have also received increasing attention in developing drugs for MDD.114 New antidepressant developments have targeted acetylcholine receptors (spurred on by muscarinic and nicotinic antagonists showing Inhibitors,research,lifescience,medical antidepressant effects) and glutamate receptors (due to rapid antidepressant effects of ketamine, an NMDA receptor antagonist).114,115 The development of radiotracer for these non-monoaminergic Inhibitors,research,lifescience,medical targets should help identify the best targets for drug development, as well as elucidation of the mechanism behind the slow onset of action of available antidepressants versus the rapid

onset of action hoped for by the novel drugs.99 Parkinson’s disease Parkinson’s disease (PD) is characterized by motor dysfunction such as resting tremor, bradykinesia, and rigidity, and also by non-motor symptoms such as depression, fatigue, and cognitive impairments. It is the second most common neurodegenerative disorder after Alzheimer’s disease.116 At post mortem, degeneration of dopaminergic neurons in mesostriatal pathways and deposits of a protein, alpha-synuclein, Inhibitors,research,lifescience,medical are typically Inhibitors,research,lifescience,medical seen. However, whilst this tells us about the end stage of the PD, molecular imaging of the dopaminergic system has been critical

in determining the development and progression of PD pathophysiology. Dopamine transporter (DAT) and vesicular monoamine transporter 2 (VMAT2) are MK0683 purchase expressed in the terminals of dopaminergic neurons and radioligand binding to these targets is an indicator of the integrity of nigrostriatal projections. Isotretinoin Lower uptake of these tracers is correlated with greater symptom severity in PD, providing evidence linking loss of terminals with the clinical expression of the disorder.117 Similarly, lower [18F]DOPA uptake in the putamen has also been correlated with greater severity of motor symptoms and greater severity of bradykinesia and rigidity.118,119 Furthermore, several studies have demonstrated the striatal [18F]DOPA uptake declines more rapidly in PD than in age-matched controls, indicating the progression of pathophysiology.120,121 [18F]DOPA PET imaging has shown that the decline in dopamine function starts in the dorsal caudate and putamen contralateral to the side with dominant motor symptoms.