Stimulants catecholaminergic

In this lecture we will be concerned by exocytosis of neurotransmitters by chromaffin cells. These cells, located above kidneys, produce the adrenaline burst which induces fast body reactions they are used in neurosciences as standard models for the study of exocytosis by catecholaminergic neurons. Prior to exocytosis, adrenaline is contained at highly concentrated solutions into a polyelectrolyte gel matrix packed into small vesicles present in the cell cytoplasm and brought by the cytoskeleton near the cell outer membrane. Stimulation of the cell by divalent ions induces the fusion of the vesicles membrane with that of the cell and hence the release of the intravesicular content into the outer-cytoplasmic region. 

Adverse effects of catecholaminergic stimulants, such as amfetamine and cocaine, fall into several categories, based on dose, time after dose, chronicity of use, and pattern of use/abuse (for example 4-5 day bingeing episodes). Adverse effects include not only responses during the period of use but also intermediate and longterm residual effects after withdrawal. For example, in some abusers once an amfetamine psychosis has developed with chronic abuse, only one or two moderate doses are required to induce the full-blown psychosis in its original form, even long after withdrawal (1). This is also evidenced by the precipitous slide to severe re-addic-tion in former abusers who are re-introduced to stimulants. 

Cardiovascular activity of 2-carboxyethylgermanium sesquioxane (Ge-132) has been studied in rats anaesthetized with urethane (i.p.). It produced a dose-related reduction in either the mean arterial pressure or the heart rate. The data indicate that Ge-132 induces both hypotension and bradycardia by promoting an activation of the parasympathetic efferent mechanisms and an inhibition of the sympathetic efferent mechanisms. On the other hand, following i.p. injection of Ge-132, increased grooming and head swaying were provoked. Thus, it appears that Ge-132 acts through the catecholaminergic mechanisms in the brain to induce locomotor stimulation in rats . ... 

Figure 10.19. False transmitters that are used for antihypertensive treatment, a a-Methyldopa passes the blood brain barrier and is decarboxylated to a-methyldopamine, which upon synaptic release stimulates presynaptic 02-receptors. b Guanethidine acts on catecholaminergic synapses in the peripheral autonomous nervous system.

The catecholaminergic and serotonergic neurons in the mesencephalon are excellent models to study the enhancer regulation since their physiological function is to supply the brain continuously with the proper amounts of monoamines that influence - activate or inhibit - billions of neurons. The significant enhancement of the nerve-stimulation-induced release of [3H]-norepinephrine, [3H]-dopamine, and [3H]-serotonin from the isolated brain stem of the rat in the presence of PEA (Fig. 3.1) or tryptamine (Fig. 3.2) is shown to illustrate the response of enhancer-sensitive neurons to endogenous enhancer substances. 

The second type of effect has been seen in studies utilizing relatively small doses of lead and monitoring lead load by measuring blood lead levels. The results of these studies are harder to interpret, but overall they suggest a stimulation of catecholaminergic function at levels of lead comparable to those found in exposed humans. The results of low-dose experiments in which drug-elicited behaviour is studied are of particular importance in the context of such borderline effects. 

Erickson JT, Millhom DE. Hypoxia and electrical stimulation of the carotid sinus nerve induce Fos-like immimoreactivity within catecholaminergic and serotoninergic neurons of the rat brainstem. J Comp Neiuol 1994 348 161-182. 

Both methylphenidate and amphetamine produce paradoxical or activity-attenuating responses in Pb-treated animals Although these di igs are generally considered catecholaminergic stimulants, amphetamine has been shown to increase ACh release. Further, methylphenidate was shown to reverse completely the Pb-mediated decrease of ACh, and Shih et al. have also shown a cholinergic effect of methylphenidate. 

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