Brain manipulability

At present, the only brain manipulation that produces a clinical state behaviorally indistinguishable from schizophrenia is the blockade of brain NMDA receptors. The primary concept underlying glutamatergic models of schizophrenia, therefore, is that the dysfunction or dysregulation of NMDA receptor-mediated neurotransmission represents the common final mechanism underlying the symptom formation in schizophrenia. Although in some individuals, the NMDA dysfunction may be related to disturbances of the receptors themselves, for other individuals, these deficits may relate more to impairments of either upstream or downstream elements involving pre- and postsynaptic neural elements respectively. 

Since biological systems can reasonably cope with some of these problems, the intuition behind neural nets is that computing systems based on the architecture of the brain can better emulate human cognitive behavior than systems based on symbol manipulation. Unfortunately, the processing characteristics of the brain are as yet incompletely understood. Consequendy, computational systems based on brain architecture are highly simplified models of thek biological analogues. To make this distinction clear, neural nets are often referred to as artificial neural networks. 

Since PD is caused by a relatively specific degeneration of the DA nigrostriatal tract and as there are specific toxins, for DA neurons, i.e. 6-OHDA and MPTP, it should be possible to produce appropriate experimental models. Certainly both toxins cause rotational behaviour in rats (Fig. 7.7) but no rodent shows a syndrome suggestive of PD. Tremor and akinesia can be seen, however, in primates after such toxins and these are being more widely used in experimental studies of PD and drug evaluation. Reserpine causes a depletion of all brain monoamines and produces motor defects in rats, which, even if not PD-like, do respond to DA manipulation. 

Since AzD is characterised by an impairment of memory, which is a normal brain function, then a consideration of which NTs and brain circuitry are implicated in the laying down and retrieval of memory may provide an indication of not only which NTs we should expect to be affected in AzD but also which need to be manipulated to therapeutic advantage. Again, most evidence points to ACh and glutamate. 

E. A. Neuwelt, ed. Implications of the Blood-Brain Barrier and Its Manipulation, Vol. 1, Basic Science Aspects, Plenum Medical Book Company, New York, 1989. 

In animal studies, high levels of cortisol have been shown to induce (increase) the activity of the enzyme tryptophan 2,3-dioxygenase in the liver, thereby decreasing the bioavailability of tryptophan to the brain. It is interesting to note that low acute doses of a number of different antidepressants inhibit the activity of this enzyme and, as a result, increase brain tryptophan concentrations, thus stimulating 5-HT synthesis (Badawy and Evans, 1982). In this way a link between the two key monoamine neurotransmitters and the hormone may be seen namely, reduced brain NA activity leads to decreased inhibition of the HPA axis, while increased levels of cortisol reduce 5-HT activity in the brain. Activation of the HPA axis has also been shown to result in tissue atrophy, in particular of the limbic system s hippocampus, and a reduction in the levels of neurotrophic factors responsible for the maintenance and optimal function of brain neurons (Manji et al., 2001). In conclusion, manipulation of the HPA axis (Nemeroff, 2002) and stimulation of neurotrophic factor activity (Manji et al., 2001) might open up new avenues for the treatment of affective disorders. 

Homo sapiens Animals with an exceptional brain able to make use of space outside themselves as well as to manipulate space inside organisms... 

Barnes, J. M. and Barnes, N. M. Neurochemical consequen-sces following pharmacological manipulation of central 5-HT4 receptors. In R. M. Eglen (ed.), 5-HT4 Receptors Brain Periphery. Berlin Springer, 1998, pp 103-126. 

Ultrasonic vocalizations are emitted by rat pups (under the age of 14 days) when they are isolated from their mother, and are thought to reflect anxiety. This measure has proven sensitive to both anxiolytic and anxiogenic manipulation of GABA neurotransmission. However, the early developmental window used is problematic, in that chronic drug administration probably results in a variety of compensatory changes not seen in adulthood, and may alter development of relevant brain systems. Indeed, in contrast to the clinical situation, the antidepressant clomipramine has acute, but not chronic, anxiolytic efficacy in this model. 

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