Opiates.Part

The locus cemleus is important for the regulation of attentional states and autonomic nervous system activity. It has also been implicated in the autonomic and stress-like effects of opiate withdrawal. A noradrenergic pathway originating from the locus cemleus which descends into the spinal cord is part of the descending inhibitory control system, which has an inhibitory effect on nociceptive transmission in the dorsal horn. 

The nucleus accumbens is part of the limbic system. It receives dopaminergic input through the mesolimbic system that originates from cell bodies in the ventral segmental area (A 10 cell group). This mesolimbic dopaminergic pathway is part of the reward pathways. Drugs of abuse (cocaine, amphetamine, opiates or nicotine) have been shown to increase the level of dopamine release in these neurons. 

Opiates and various derivatives are commonly used to treat diarrhea, partly because they inhibit electrolyte secretion (Suzuki et al., 2000 Tumberg, 1983). Other phytochemicals counter the secretory responses to cholera toxin (Oi et al., 2002). An example would be the decreased chloride secretion caused by proanthocyanide and the ability to inhibit the secretory diarrhea caused by cholera toxin, but only if administered first (Hor et al., 1995). In the light of the co-transport of water and electrolytes by carriers of glucose... 

The neuroehemical sites for psyehomotor stimulant reward are likely to be the presynaptic dopamine terminals located in the region of the nucleus aeeumbens, frontal cortex, and other forebrain structures that originate in the ventral tegmental area. Note, however, that intraeranial self-administration of eoeaine is elicited from the frontal cortex, but not from the nucleus aeeumbens (Goeders and Smith 1983). Thus, eoneomitant activation of structures other than the nucleus accumbens may be an important part of the circuitry involved in initiation of cocaine intravenous self-administration, as has been hypothesized for the opiates (Smith and Lane 1983 Smith et al. 1982). 

The noradrenergic neurons of the locus ceruleus have provided a useful model system for the study of opiate addiction (see Ch. 56). Acutely, opiates inhibit these neurons, in part by inhibiting the cAMP pathway via inhibition of adenylyl cyclase. Chronically, these neurons become tolerant to opiates that is, their firing rates recover toward normal levels with continued exposure to the... 

Increasing evidence indicates that a chronic opiate-induced upregulation of the cAMP pathway, manifested by increased concentrations of adenylyl cyclase, PKA and several phosphoprotein substrates for the protein kinase, contributes to opiate tolerance, dependence and withdrawal exhibited by locus ceruleus neurons [66]. This upregulated cAMP pathway can be viewed as a homeostatic response of the neurons to persistent opiate inhibition of the cells. In the chronic opiate-treated state, the upregulated cAMP pathway helps return neuronal firing rates to control levels, i.e. tolerance. Upon abrupt removal of the opiate via the administration of an opiate receptor antagonist, the upregulated cAMP accounts for part of the withdrawal activation of the cells. 

Chronic opiate-induced upregulation of the cAMP pathway appears to be mediated in part by CREB chronic opiate administration increases CREB expression mice deficient in CREB show attenuated physical opiate dependence and withdrawal and selective reductions of CREB in the locus ceruleus prevent upregulation of specific components of the cAMP pathway in response to chronic opiate administration [66]. This latter action is associated with attenuation of the electrical excitability of locus ceruleus neurons and of physical opiate dependence and withdrawal. 

There are two main treatments for the opiate withdrawal syndrome. One is replacement therapy with methadone or other X agonists that have a longer half-life than heroin or morphine, and produce mild stimulation rather than euphoria. They also produce cross-tolerance to heroin, lessening heroin s effect if patients relapse. Withdrawal is also treated with the 0C2 agonist clonidine, which inhibits LC neurons, thus counteracting autonomic effects of opiate withdrawal — such as nausea, vomiting, cramps, sweating, tachycardia and hypertension — that are due in part to loss of opiate inhibition of LC neurons. 

Loperamide is also structurally related to meperidine and its mechanism of action is like diphenoxylate. Gastointestinal motility is decreased by inhibition of the contractions of the longimdinal as well as the circular musculature, and the activity of this agent is at least in part mediated by its affinity for opiate receptors. As it hardly crosses the blood-... 

Symptom patterns those with alternating constipation and diarrhoea and predominant constipation may benefit from high fibre diets (although excess fibre may bloat). Those with predominant diarrhoea may require simple peripheral opiate agonists (loperamide), but may also be helped by raised fibre intake. Pain may respond in part to explanation that it does not indicate serious illness and in part to spasmolytic therapy with anticholinergic agents which... 

The part played by endogenous opioid systems in the regulation of these various physiological and behavioral functions has led to the experimental application of opiate antagonists in psychiatric disorders. This chapter focuses on autism and self-injury, which are two potential indications for opiate antagonists in pediatric populations. In adults, treatment with opiate antagonists has shown to be useful in the relapse prevention of alcoholism as part of a comprehensive treatment approach (Anton et ah, 1999, 2001). 

There are many peripheral organs that possess enkephalin opiate receptors the ileum, the most distal part of the small intestine, and the vas deferens are the most significant. The receptors in the ileum are responsible for the antidiarrheal activity of opiates. This is also the explanation for the severe constipation that may occur when people use opiates for pain relief. 

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