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DL-PFC viagra extra dosage 120 mg free shipping, dorsolateral prefrontal cortex; IC viagra extra dosage 150mg visa, internal capsule; S, shell; Snc, sub- stantia nigra, zona compacta; Snr, substantia nigra, zona reticulata; VTA, ventral tegmental area. Therefore, unlike acute exposure to stressful or noxious Increasing NO in the striatum by infusion of the substrate stimuli, chronic stress actually attenuates DA neuron base- for the synthetic enzyme nitric oxide synthetase (NOS), line activity. Such a decrease in baseline activity could enable coupled with striatal or cortical stimulation, was found to the system to show a magnified response to activating stim- increase the firing rate of striatal neuron DA neurons. This uli, thereby producing a sensitized DA response. In contrast, NOS inhibitors failed to affect REGULATION OF DA RELEASE baseline DA cell firing but did increase their response to stimulation (34); therefore, NO signaling in the striatum DA appears to be released by multiple factors within its facilitates DA neurotransmission by modulation of cortico- postsynaptic target; moreover, once it is released, there are striatal and striatonigral pathways. NO also appears to have several mechanisms that can modulate its site of action. In a role in regulating terminal DA release (see the following). Carbon fiber recordings, which plays a role both in acute behavioral responses and adapta- allow rapid measurement of DA overflow, show that stimu- tions to chronic stressful conditions. Although the nor- lation of DA axons causes rapid release of transmitter. More- adrenergic system has played a major role in these processes, over, the release varies with tissue content, with PFC show- recent evidence supports a role for the DA system as well. DA released by impulse differential increases in DA dynamics depending on the flow is then rapidly removed via the DA transporter, because brain regions involved. Thus, stressful stimuli tend to cause mice with knockouts of this transporter exhibit 300 times the largest increase in DA levels in the PFC region, with longer clearance half-life compared to controls (42). The markedly smaller changes in the limbic and dorsal striatal amount of DA released by impulses appears to depend on regions (35); however, this relationship is altered by lesions several factors. Previous volumes in the Generations of of different nuclei. Thus, stress causes release of DA in the Progress series have detailed how DA release can be modu- amygdala (36), and lesions of the amygdala tend to block lated by both synthesis- and release-modulating autorecep- stress-induced increases in PFC DA levels (37).

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Such paradigm design may similar pattern of regional brain activity cheap viagra extra dosage 120 mg on line, but in the opposite prove useful in investigation of affective illnesses such as direction discount viagra extra dosage 130mg with amex, in the normals during induced sadness. For disease is still in its infancy because of only recent develop- depressed patients, the increases in dorsal cortical regions ment of some appropriate task paradigms; however, the area may reflect increased cognitive function in the remitted has substantial promise. The decreases in the subgenual anterior cingulate as used to map changes in brain activity in depressed patients and normal controls while viewing a film segment chosen symptoms resolve appears more complicated. The depressed patients had signifi- possible to conclude from the data presented in Mayberg cantly more activation in areas of the prefrontal cortex. In- and associates (122) that the depressed state reflects an in- creased activation in the prefrontal cortex of the depressed creased and abnormal functioning of the subgenual cingulate cortex could be secondary to increased processing of the that returns to baseline during remission. For many tasks increased Drevets and colleagues (3) clearly showing decreased metab- prefrontal activation accompanies an increase in task diffi- olism in the subgenual cingulate during a depressive episode culty; however, several issues, including the potential for needs to be reconciled. One explanation is that the decreased differences in cognitive response or attention level to the activity is conceivably an actual increase in functional activ- film being shown, must temper the interpretation of this ity that only appears decreased on PET imaging owing to work. Further fMRI work on the processing of emotional partial volume effects. This region was also reported by stimuli in depressed patients is ongoing and will certainly Drevets and colleagues to have sizable decreases in volume shed more light on this fascinating area of research. Some consensus has begun to emerge pointing to abnor- Nevertheless, the subgenual cortex and adjacent anterior Chapter 74: Imaging of Affective Disorders 1073 cingulate appear to play an important role in emotional regulation and expression. Molecular Imaging of Neurotransmitter Systems in Affective Disorders Numerous hypotheses have been proposed relating mono- amine systems and depression. Serotonin, dopamine, and norepinephrine have all been implicated to various degrees in the behavioral changes and treatment of depression. Of these three, reports indicating a constellation of specific se- rotonergic dysfunctions in major depressive disorders have been the most convincing. For this reason, much effort in A the imaging community has been focused on developing tools for imaging different aspects of the serotonergic system in vivo. Generally, these tools have involved the develop- ment and validation of radioligands specific for serotonin receptor subtypes (with more than 14 serotonin receptors isolated to date); however, alternative approaches to image serotonergic function have been reported as well. A report by Mann and co-workers (123) demonstrated reduced sero- tonin responsivity in depressed patients. In that work, fenfl- uramine, an indirect serotonin agonist, was used as a phar- macologic challenge and FDG PET imaging was used to image the brain responses.

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