NEURO 1

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NEURO 1
Dopamine is known to regulate emotion, reward, cognition, memory, endocrine functions and motor control.
The ability of striatal serotonergic neurons and glia to convert L-DOPA to dopamine may explain why L-DOPA continues to be effective, albeit to a lesser extent, in advanced stages os Parkinson’s disease when fewer dopaminergic neurons are remaining in the substantia nigra
Depression is one of the most costly brain diseases in the world in terms of pain anda suffering, lost work, and mostality from suicide. Depression is not only common but also appears to be increasing in frequency and to be occuring ar na earlier age of onset. Disorders of mood are increasingly understood to be a group of systemic illnesses involving central neurotransmitter imbalances ans neuroanatomical disruptions, along with potential dysregulation of imune, autonomic, endocrine, and cardiovascular function. 
Chronicity leads to progressive treatment resistance.
About 30% of patients with depression do not meet typical response criteria to na initial course of antidepressants, and futhermore the majority of patients are not symptom free with monoterapy. Additionaly, 10-20% os depressed patients do not tolerate an initial trial of antidepressant medication. Thus, 25-30% of patients who complete an adequate trial of an approved antidepressant do not have an adequate response.
It is now clear based on various lines of reasoning and empirical data that changing the set point of monoamine transmission does not fully explain antidepressant action but plastic changes in the limbic target áreas of monoamine neuron projections are important in the mechanism of action of antidepressants.
The locus ceruleus(LC) is a compact nucleus containing noradrenergic neurons as well as peptide neurotransmitters that influence its acivity. LC neurons can fire in either a tonic or phasic pattern and electrotonic coupling between neurons can be inffluences by neurotransmitters. Release of NE can be accompained by corelease of the peptide neurotrannsmitter galanin, which is inhibitory and may alter the firing rate of dopamine neurons, thus altering its hedonic tone. Shifts in the pattern of firing of LC neurons are thought to be of great importance in understanding attentional processes, often disrupted in depression.
Clinical evidence also suggests noradrenergic system involvement in severe depression. Levels of the rate-limiting enzyme for catecholamine synthesis, tyrosine hydroxylase, are upregulated post-mortem in suicide victims, and chronic treatment with all of classes of antidepressants reduces activity of TH in rodents.
Neuroplasticity and Use-Dependent Activity
Preliminary insight into the mechanism underlying na organism’s ability to adapt to nd learn from its enviroment began with the observation that neurotransmitter stimulation of neurons alters gene transcription. Use-dependent plasticity is seen in neuronal networks and synapses, and the downstream expression of transcription factors that sculpt neural circuits is critical to our understanding of mood states and antidepressant action. The term “neuroplasticity” subsumes functional changes in the nervous system and can be discussed at diferente levels. Plasticity can be at the level of synaptic anatomy and connectivity – changes in synaptic plasticity via alterations dendritic function, synaptic remodeling, synaptogenesis, ou neurogenesis. Plasticity can also refer to changes in long-term potentiation or be discussed in terms of behaviorial plasticity. Neurotransmitters, neuromodulators, and hormones that influence intracelular signaling cascades mediate these functional changes. Recent morphometric studies and pharmacological studies suggest the possible importante of neuroplastic events in eitiology and treatment for affetive disorders.
Characterizing drug target effects on neurotransmitters, transcription fator levels, or brain circuitry implicated in depression can then validate novel drug targets indentified. Also, is drugs with known psychotropic effects Interact or regulate expression of a candidate gene or protein, this would provide further confirmation of the target’s relevance.