Serotonergic neurons, effects

Both these predictions are borne out by clinical experience despite the snag that only MAOb is found in serotonergic neurons (Saura et al. 1996). So far, there is no explanation for this anomaly. However, the lack of a tyramine-induced pressor effect with moclobemide probably owes more to the fact that it acts as a reversible inhibitor of MAOa (RIMA) than to its isoenzyme selectivity. Its reversible inhibition of MAOa means that, should tyramine ever accumulate in the periphery, it will displace... 

Figure 20.6 Schematic representation of the effects of 5-HT reuptake inhibitors on serotonergic neurons, (a) 5-HT is released at the somatodendritic level and by proximal segments of serotonergic axons within the Raphe nuclei and taken up by the 5-HT transporter. In these conditions there is little tonic activation of somatodendritic 5-HTia autoreceptors. At nerve terminals 5-HTib receptors control the 5-HT synthesis and release in a local manner, (b) The blockade of the 5-HT transporter at the level of the Raphe nuclei elevates the concentration of extraneuronal 5-HT to an extent that activates somatodendritic autoreceptors (5-HTia). This leads to neuronal hyperpolarisation, reduction of the discharge rate and reduction of 5-HT release by forebrain terminals, (c) The exposure to an enhanced extracellular 5-HT concentration produced by continuous treatment with SSRIs desensitises Raphe 5-HTia autoreceptors. The reduced 5-HTia function enables serotonergic neurons to recover cell firing and terminal release. Under these conditions, the SSRI-induced blockade of the 5-HT transporter in forebrain nerve terminals results in extracellular 5-HT increases larger than those observed after a single treatment with SSRIs. (Figure and legend taken from Hervas et al. 1999 with permission)...

Schmidt, C.J., and Taylor, V.L. Direct central effects of acute methylenedioxymethamphetamine on serotonergic neurons. Eur J Pharmacol 156 121-131, 1988. 

Effects of Neurotoxic Amphetamines on Serotonergic Neurons immunocytochemicai Studies... 

Ricaurte, G.A. Fomo, L.S. Wilson, M.A. DeLanney, L.E. Irwin, I. Molliver, M.E. and Langston. J.W. ( )methylenedioxymethamphetamine (MDMA) exerts toxic effects on central serotonergic neurons in primates. Abstr Soc Neurosci 13 905, 1987. 

The most consistent changes have been observed in the DA systems with more variable effects on norepinephrine (NE) and serotonergic neurons. 

Haigler, H. J., and Aghajanian, G. K. (1974) Lysergic acid diethylamide and serotonin A comparison of effects of serotonergic neurons and neurons receiving a serotonergic input. J Pharmacol. Exp. Ther., 188 688-699. 

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