Neuron system

Unlike aniracetam, pramiracetam does not appear to interact with dopaminergic, serotonergic, or adrenergic neurotransmission (72). The agent inhibits prolylendopeptidase in certain brain areas, but its inhibition constant, iC, is only 11 ]lM (69). The absence or weak activity of this compound with various neuronal systems appears to make it less likely to be of significant therapeutic value than other members of this class of agents. 

Drug addiction is a pathological behavioral syndrome that has to be strictly separated from physical dependence. An individual can be physically dependent on a drug without being addicted to it and vice versa. Transient neuroadaptive processes underlie physical dependence and tolerance to a drug, whereas persistent changes within specific neuronal systems underlie addictive behavior. 

Chronic administration of opiates and alcohol leads to physical dependence a phenomenon, which is only weakly expressed following chronic administration of psychostimulants or other drugs of abuse. Physical dependence results from neuroadaptive intracellular changes to an altered pharmacological state. Abstinence from chronic opiate or alcohol use leads to a variety of physiological and psychological withdrawal symptoms based on these adaptations of the neuronal system. 

The action of 5-HT on brain neuronal systems is complex depending on the neurons involved, it can induce inhibition or excitation. Experiments with iontophoretic application of LSD to neurons have shown that 5-HT-induced excitation is invariably blocked by LSD, whereas LSD mimics inhibition at sites where 5-HT exerts an inhibiting effect (Aghajanian et al. 1987 Martin and Sloane 1986). Tryptamine itself is found in all major regions of... 

Martin WR, Sloan JW Relationship of CNS tryptaminergic processes and the action of LSD-like hallucinogens. Pharmacol Biochem Behav 24 393-399, 1986 McCall R Effects of hallucinogenic drugs on serotoninergic neuronal systems. Pharmacol Biochem Behav 24 359-363, 1986... 

Chemokines play an important role in the regulation of synaptic activity in the brain. Such properties of chemokines have been described in several neuronal systems (For review Ragozzino 2002). In this chapter we will exclusively focus on two examples to illustrate the neuromodulatory effects of chemokines. 

Figure 1.8 Some basic neuronal systems. The three different brain areas shown (I, II and III) are hypothetical but could correspond to cortex, brainstem and cord while the neurons and pathways are intended to represent broad generalisations rather than recognisable tracts. A represents large neurons which have long axons that pass directly from one brain region to another, as in the cortico spinal or cortico striatal tracts. Such axons have a restricted influence often only synapsing on one or a few distal neurons. B are smaller inter or intrinsic neurons that have their cell bodies, axons and terminals in the same brain area. They can occur in any region and control (depress or sensitise) adjacent neurons. C are neurons that cluster in specific nuclei and although their axons can form distinct pathways their influence is a modulating one, often on numerous neurons rather than directly controlling activity, as with A . Each type of neuron and system uses neurotransmitters with properties that facilitate their role...

Moore, RY and Bloom, FE (1978) Central catecholamine neuron systems, anatomy and physiology of the dopamine system. Ann. Rev. Neurosci. 1 129-169. 

Coupling of the receptors is very similar with all three coupling to Gq and increasing IP3/DAG and in a number of neuronal systems it has been shown that the receptors produce slow depolarising responses via the closing of potassium channels. 

However, experience proves that depression can be reversed by drugs that augment serotonergic and noradrenergic transmission (and reinstated by a deficit in the synthesis of these monoamines). These, then seem to be crucial targets that ultimately determine mood. This would explain why, despite numerous neurochemical options for the causes of depression, all antidepressants developed so far (and even those discovered by chance) target these neuronal systems. Whatever the cause of depression, therefore, its relief seems to rest on appropriate secretion of these monoamines. This would be entirely... 

Most of the work has been based on opioids since it is the easiest system to manipulate as administration of the antagonist, naloxone, precipitates withdrawal. Flere, the idea that physical dependence results from opposing changes in the neuronal systems depressed by the drug of dependence is borne out by consideration of the acute effects of an opioid and the withdrawal symptoms. They are mirror images of each other ... 

My second question is this You mentioned ferrfluramine. I presume you used the racemic mixture, which would mean that in the brain you would have both R and S fenfluramine and R and S norfenfluramine present. And since these differ widely in their effects on dopamine versus serotonin neuronal systems, have you studied individual enantiomers of either fenfluramine or norfenfluramine ... 

The actions of amphetamine are widespread throughout the brain. Amphetamine s immediate effect is to alter the release of monoamines in a dose-dependent manner that is specific for each monoamine transmitter neuronal system. The net effect of amphetamine on monoamine release is complex, with some mechanisms tending to increase monoamine release (e.g., blockade of reuptake and nonimpulsedependent release), and several mechanisms tending to diminish release (e.g., activation of somatodendritic and terminal autoreceptors). 

Molliver, M.E. Serotonergic neuronal systems What their anatomic organization tells us about function. J Clin Psychopharmacol [Suppl] 7 3-23, 1987. 

Moore, R.Y. The anatomy of central serotonergic neuron systems in the rat brain. In Jacobs, B.L., and Gelperin, A., eds. Serotonin Neurotransmission and Behavior. Cambridge, MA MIT Press, 1981. pp. 35-71. 

RESPONSE Perhaps I can bridge the dispute by suggesting it is probably going to vary among neuronal systems. There may be systems in which you must have a lot of depletion to see a functional change, and there may be others where it doesn t take very much. 

Rajendren G., Dudley C. and Moss R. (1993). Influence of male rats on the LHRH neuronal system in the female role of vomeronasal organ. Neuroendocrinology 57, 898-906. 

Reger R.L., Gerall A.A., et al. (1987). LHRH neuronal system in the accessory olfactory bulb of the prairie vole, Microtus ochrogaster. Neurosci Abs 13, 993. 

This laboratory, as well as others, has shown unequivocally that PCP affects a variety of parameters related to neurotransmission in several neuronal systems. This paper has focused on evidence for the involvement of dopaminergic, cholinergic, and glutama-tergic pathways, and evidence of their interactions in the rat striatum. However, the effects of PCP undoubtedly involve other neuronal systems in other brain areas. Thus, it must be borne in mind that the data discussed in this paper cannot possibly account for the more complex behavioral effects of PCP. 

The endogenous analgesic system is a built-in neuronal system that suppresses transmission of nervous impulses in the pain pathway. It functions by way of the following neurotransmitters produced in the CNS ... 

Watanabe, T., Taguchi, Y Shiosaka, S. et al. (1984). Distribution of the histaminergic neuron system in the central nervous system of rats a fluorescent... 

Moore, R. Y. Bloom, F. E. (1979). Central catecholamine neuron systems anatomy and physiology of the norepinephrine and epinephrine systems. A. Rev. Neurosci. 2, 113-68. 

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