Neurotransmitter activity

Figure 1. A depiction of the several different ionic currents necessary for the acute function of neuromuscular transmission in the skeletal motor and the efferent autonomic nervous system. The boxed current designations are associated, by the arrows, with those cellular regions where their physiological role is most evident, although these currents often exist in other regions of the cell. = neurotransmitter-activated current ...

There have been many references in this book to the role of neurotransmitters in the control of CNS excitability. It is therefore appropriate, but possibly foolhardy, to see if the two natural extremes of that excitability, namely sleep and waking, can be explained in terms of neurotransmitter activity. Of course, these states are not constant our sleep can be deep or light and, even when we are awake, our attention and vigilance fluctuate, as the reading of these pages will no doubt demonstrate. Also, the fact that we sleep does not mean that our neurotransmitters are inactive this would imply that sleep is a totally passive state, whereas all the evidence suggests that it is an actively induced process, subject to refined physiological control. 

Altered release. Tetanus is an infectious disease caused by the bacterium Clostridium tetani. This bacterium produces a neurotoxin active on inhibitory synapses in the spinal cord. Motor neurons, which supply skeletal muscle and cause contraction, have cell bodies that lie in the spinal cord. Under normal circumstances, these motor neurons receive excitatory and inhibitory inputs from various sources. The balance of these inputs results in the appropriate degree of muscle tone or muscle contraction. Tetanus toxin prevents the release of gamma amino butyric acid (GABA), an important neurotransmitter active at these inhibitory synapses. Eliminating inhibitory inputs results in unchecked or unmodulated excitatory input to the motor neurons. The resulting uncontrolled muscle spasms initially occur in the muscles of the jaw, giving rise to the expression lockjaw. The muscle spasms eventually... 

For any substance to serve effectively as a neurotransmitter, it must be rapidly removed or inactivated from the synapse or, in this case, the neuroeffector junction. This is necessary in order to allow new signals to get through and influence effector tissue function. Neurotransmitter activity may be terminated by three mechanisms ... 

An unanswered question about adenosine is how this inhibitory neurotransmitter activates the ventrolateral preoptic area of the hypothalamus (VLPO), which contains a population of sleep-active neurons and is hypothesized to be... 

Deficiency of essential amino acid precursors in the diet can cause a dysregulation of neurotransmitter activity (e.g, L-tryptophan deficiency causes a decrease in 5-HT and melatonin synthesis and activity). Deficiency in essential fatty acids (e.g, omega-3 fatty acids) can cause a dysregulation of neurottansmitter... 

An inhibitory neurotransmitter activates an inhibitory G-protein thereby leading to a reduction in cAMP synthesis. 

The alterations in neurotransmitter activity which trigger or accompany the onset of natural sleep and distinguish slow wave or non-REM from REM sleep, provide one of the most compelling arguments in favour of chemical neurotransmission being specifically involved in mechanisms of conscious awareness. For an extensive review on neurochemistry and sleep, see Gottes-man (1999). 

This chapter is concerned with the neurochemical basis of developmental disability which is considered here in two forms the globally delayed or halted development seen in mental retardation, and the more circumscribed pattern of disordered development of autism. A range of deficits of important key aspects of consciousness are apparent in both conditions. Of particular relevance to consciousness are the cognitive and behavioural impairments in attention, concentration, memory, information processing and social behaviour which are commonly present. Consideration of aberrant neurotransmitter activities in these developmental deficits may provide insights into the role of neurotransmitters in consciousness. 

Several therapeutic agents, especially those that affect neurotransmitter activity (both agonist and antagonist) are often associated with ED. Many such reports have been anecdotal, although 25% of ED may be drug-related. Several classes of drugs have been associated with ED (Table 64.1). The mechanism or mechanisms of... 

Miscellaneous CNS drugs bupropion,1 fluoxetine,1 zonisamide,1 atomoxetine1 Alterations in CNS neurotransmitter activity... 

An agonist and an antagonist in the same molecule provide quite a new dimension to therapeutics. This concept has led to proposals that partial agonists could treat not only states that are theoretically deficient in full agonist but also states that theoretically have an excess of full agonist. An agent such as a partial agonist may even be able to treat simultaneously states that are mixtures of both excessive and deficient neurotransmitter activity. 

Stahl, S.M. (1999) Molecular neurobiology for practicing psychiatrists, part 2 how neurotransmitters activate second messenger systems. Journal of Clinical Psychiatry 60(10), 647—8. 

Catecholamine neurotransmitters are subsequently inactivated by enzymic methylation of the 3-hydroxyl (via catechol-O-methyltransferase) or by oxidative removal of the amine group via monoamine oxidase. Monoamine oxidase inhibitors are sometimes used to treat depression, and these drugs cause an accumulation of amine neurotransmitters. Under such drug treatment, simple amines such as tyramine in cheese, beans, fish, and yeast extracts are also not metabolized and can cause dangerous potentiation of neurotransmitter activity. 

Presynaptic receptor that is activated by a neurotransmitter from an adjacent neuron the type of neurotransmitter activating the heteroceptor differs from that released from the axon. 5-Hydroxyindoleacetic acid, the main metabolite of 5-hydroxytryptamine (serotonin) formed by monoamine oxidase. 

The effects of cocaine or its withdrawal on neurotransmitter activity have been evaluated in several studies. Although changes in dopaminergic activity appear to be associated with early cocaine abstinence, extrapyramidal symptoms (due to alterations in dopamine functioning) have only infrequently been reported in cocaine users. 

Also important in understanding the function of the nervous system are the one-way flow of information across synapses and stimulatory versus inhibitory impulses Most synapses in the CNS will conduct an impulse (usually via a neurotransmitter) in one direction only that is, from the axon of the presynaptic neuron to the dendrite or cell body (soma) of the postsynaptic neuron (see Figures 1.2 and 1.3). This unidirectionality is critical in preserving the integrity of the information flow in the CNS. A particular postsynaptic neuron will have anywhere from 10,000 to 200,000 terminals, or receptor sites, that interact with presynaptic neurons. These terminals are activated by neurotransmitters. Activating some terminals will cause the postsynaptic neuron to fire an impulse to its neighbor neurons. When other terminals are activated, the same postsynaptic neuron will be especially quiet and will not fire off any impulses. This concept of stimulation versus inhibition and inhibitory impulses from one neuron to another is key in our discussion of mental illness and its treatment. 

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