Neurochemical pathway

Nicotinic cholinergic receptors are located on cells that release a wide variety of transmitters (see chapter by Barik and Wonnacott, in this volume), so that nicotine interacts with multiple neurochemical pathways. The roles of cholinergic, dopaminergic, and endogenous opioid systems in physical dependence and withdrawal have been most thoroughly studied and documented. Research on the role of other transmitters and neurochemical mechanisms is rather scattered. Overall, however, research with rodent models of physical dependence has provided a wealth of potential targets for experimental treatments to aid smoking cessation. 

Pharmacology has provided powerful tools to characterize the neurochemical pathways of stress and anxiety in the brain, and how these pathways are involved in the pathophysiology and treatment of anxiety disorders. In the past, this work has largely focused on classical neurotransmitter systems, including the synthesis, release, and metabolism of monoamines and receptor subtypes that control presynaptic release of neurotransmitters and their postsynaptic effects. Increasing the specihcity of drugs but also the combination of mechanisms has been pursued to improve anxiolytic drugs. 

To date, two types of major depression have been postulated. The first is often referred to as endogenous or melancholic depression. In this type of major depression, symptoms of depressed mood are related directly to internal biologic factors such as neurotransmitter dysfunction (Kaplan Sadock, 1990 Tierney et al., 1997). Electroconvulsive therapy (ECT), referred to historically as shock treatments, is often considered an endogenous treatment. Here, direct (biologic) stimulation of the neurotransmission process is the treatment strategy. Similar to ECT, antidepressant medications also are successful in lifting endogenous depression, with the major difference that they affect the neurochemical pathways chemically rather than electrically (Maxmen Ward, 1995). 

Tun C, Guo W, Nguyen H, Yun B, Libby RT, Morrison RS, Garden GA (2007) Activation of the extrinsic caspase pathway in cultured cortical neurons requires p53-mediated down-regulation of the X-linked inhibitor of apoptosis protein to induce apoptosis. J Neurochem 102 1206-1219... 

Effects in Laboratory Animals. As highlighted in other chapters, the central toxicities during and after repeated stimulant bingeing may be related to neuronal or terminal destruction and/or depletion of neurotransmitter in the brain. In monkeys and cats, the report by Duarte-Escalante and Ellinwood (1970) of neuronal chromatolysis associated with decreased catecholamine histofluorescence following chronic METH intoxication has been followed by extensive neurochemical demonstrations of damage to the monoamine pathways by chronic stimulants (Seiden and Ricaurte 1987). 

Without interruption, the neurochemicals ultimately lead to a firing of the unmyelinated or thinly myelinated afferent neurons. This sends messages along the pain pathway in the periphery and transfers the pain message to the central nervous... 

Leurs, R., Traiffort, E., Arrang, J. M. et al. (1994). Guinea pig histamine HI receptor. II. Stable expression in Chinese hamster ovary cells reveals the interaction with three major signal transduction pathways. J. Neurochem. 62, 519-27. 

Haycock, J.W. Multiple signaling pathways in bovine chromaffin cells regulate tyrosine hydroxylase phosphorylation at Serl9, Ser31, and Ser40. Neurochem. Res. 18 15, 1993. 

Ben Yoseph, O., Camp, D. M., Robinson, T. E. etal. Dynamic measurements of cerebral pentose phosphate pathway activity in vivo using [ 1,6-13C2,6,6-2H2] glucose and microdialysis. /. Neurochem. 64 1336-1342,1995. 

Nadler, J. V. The recurrent mossy fiber pathway of the epileptic brain. Neurochem. Res. 28 1649-1658, 2003. 

Cassel, J. C., Duconseitle, E., Jeltsch, H. and Witt, B. (1997) The fimbria-fomix/cingular bundle pathways a review of neurochemical and behavioural approaches using lesions and transplantation techniques. Prog. Neurobiol. 51, 663-716. 

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