on of the negative feedback mechanism will prevent downregulation of AT1 receptor. This ultimately leads to hyperactive renin-angiotensin and sympathetic nervous systems that may contribute to blood pressure increase in hypertensive rats. Studies supporting this show that inhibitory effects of NE on AT1 receptor expression in brain neurons of Wistar-Kyoto rats is absent in neurons of spontaneously hypertensive rats."(Ad Verbatum) Figure. 21 a serotoninergic neuron displaying 5-HT1A AutoreceptorsDue to the dual location of 5-HT1A receptors(Fig. 21), regulation of serotoninergic transmission occurs. 5-HT1A located on serotoninergic neurones acting as somato – dendritic autoreceptors, and on targets of serotoninergic projections which correspond to post synaptic receptors. Two opposing effects occur from the stimulation of 5-HT1A in the raphe nuclei compared to regions such as the limbic system. Agonists of 5-HT1A acting at the somato – dendritic autoreceptors inhibit electrical activity of the serotinergic neurones therefore reducing the level of serotoninergic neurotransmission. However in contrast to this occurrence, where serotoninergic projections target the post synaptic level, agonists of 5-HT1A reproduce the effect by transmitting 5-HT from the serotoninergic terminals, overall enhancing the receptor dependant 5-HT1A neurotransmission. If an 5-HT1A antagonist is administered blockade of serotoninergic neurotransmission mediated through the post synaptic 5-HT1A receptors occurs but an increase in electrical activity of serotoninergic neurones also occurs due to a blockade at the somato-dendritic 5-HT1A autoreceptors. Not all 5-HT1A antagonists increase electrical activity of serotoninergic neurones this is due to their variable intrinsic efficacies in receptor blockade. An experiment carried out to demonstrate this (FORNAL et al. 1994a,b) spiperone and WAY100635 significantly increased the serotonergic neuronal firi...
