Monoaminergic neurons, effects

TABLE 1. Effects of amphetamine-related compounds on monoaminergic neurons... 

Effects In Humans. Neither postmortem nor functional cerebrospinal fluid (CSF) studies in humans provide firm evidence for similar, long-term damages or alterations to monoaminergic neurons in chronic stimulant abusers. In part, the lack of demonstrable neurochemical changes may well be due to the obvious preclusion of well-controlled prospective experimentation in humans, as well as to variability in critical variables (e.g., individual sensitivity or pattern of abuse) encountered in clinical research. Possible relationship of the various complications of stimulant abuse including hyperpyrexia, seizure, anoxia, and metabolic exhaustion to neuronal chromatolysis, terminal destruction, and monoamine and enzymatic depletion have not been systematically explored in human autopsy eases. It should be also noted that, under nonperturbed conditions, overt behavioral deficits are rare in... 

The possible effects of hallucinogens on central monoaminergic neurons were first explored by Freedman (34), who discovered that a single injection of LSD increases 5-HT levels in the rat brain, whereas its inactive congener BOL fails to affect brain 5-HT. Since this change is associated with a decrease in the concentration of the main metabolite of 5-HT, 5-hydroxyindole acetic acid (5-HIAA) (Fig. 1), Rosecrans et al. (98) postulated that LSD administration in... 

Additional neuropharmacological changes that may contribute to the clinical effects of tricyclic antidepressants include indirect facihtation of 5-HT (and perhaps DA) neurotransmission through excitatory heteroreceptors on other monoaminergic neurons, or desensitized, inhibitory autoreceptors, as well as D autoreceptors. Activated release of 5-HT and DA may, in turn, lead to secondary down-regulation of 5-HTj autoreceptors, postsynaptic S-HT receptors, and perhaps D autoreceptors and postsynaptic Dj receptors. 

Phenothiazines and butyrophenones may cause various movement disturbances in man. Dystonia in children and young adults and parkinsonism or restlessness in older subjects may occur during treatment and are reversible. The facial dyskinesia which may occur in elderly subjects, especially those with evidence of brain damage, is often irreversible (see ref. 225 for review). Unlike reserpine, these substances have little effect on brain amine levels in animals. They behave as if they block amine receptors so that there is a compensatory activation of monoaminergic neurones with increased but functionally ineffective release of amines into the synaptic cleft. Thus,... 

There is good evidence that the facilitation of peripheral sympathetic nervous system transmission prcxluced by the amphetamines also occurs in the CNS.The possibihty that amphetamines act indirectly (i.e., by releasing monoamines) at monoaminergic synapses in the brain and spinal cord seems likely. However, amphetamine has effects beyond displacement of catecholamines these include inhibition of neuronal amine uptake, direct stimulation of dopamine and serotonin receptors, antagonism of catecholamine action at certain subtypes of adrenoceptors, and inhibition of monoamine oxidase. Interestingly, none of these actions explains the therapeutic benefit of the amphetamines in hyperkinetic children. 

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