Recientes avances en la configuración de la neurotransmisión serotoninérgica / Recent advances in the serotonin neurotransmitters configuration

Serotonin (5-HT) is, from a filogenetic point of view, one of the older neurotransmitter. It has been isolated more than 40 years ago. But only less than 5 per cent belongs to central 5-HT. In the 60's researchers focused their works on the intracellular processes (synthesis, storage, re-uptake, catabolism and the role of the enzime Tryptophane-hydroxilase). They also described some serotonin EEG effects. In the 70's the role of other aminoacids inhibiting Tryptophan, and therefore 5-HT synthesis, was studied. But it is in the early 80's when the 5-HT receptors and the second messanger mechanisms began to draw their attention. There are at least seven 5-HT receptors described until 1994, each one of them with several subtypes. Clinical uses of their agonists and antagonists appear to be useful in many psychiatric disorders. This paper makes a review of the 5-HT receptor Arboretum and its clinical implications, and the participation of the neurotransmitter in affective and anxiety disorders, phsychosis and other CNS illnesses. We also wanted to examine the use of SSRI and inespecific serotonin reuptake inhibitors, atypical antipsychotics with serotonin mechanisms of action, and other serotonergic drugs acting on migraine, aggressive behavior, eating disorders, adictions and dementia.

Serotonergic modulation of footshock induced aggression in paired rats.

Footshock induced aggression (FIA) was induced in paired rats and three paradigms of aggressive behaviour were recorded, namely, latency to fight (LF), total period of physical contact (TPP) and cumulative aggression scores (CAS). The effects of increasing or decreasing central serotonergic activity, by using a number of pharmacological agents with well defined effects on rat brain serotonin, were investigated on FIA and on FIA augmented by apomorphine, a dopamine receptor agonist. The results show that centrally administered serotonin, the serotonin precursor, 5-hydroxytryptophan administered with clorgyline, a selective MAO A inhibitor, quipazine, a serotonin receptor agonist, and fluoxetine, a selective inhibitor of neuronal re-uptake of serotonin, attenuated all paradigms of FIA and apomorphine induced potentiation of FIA. On the contrary, the other re-uptake inhibitor used, citalopram, appeared to have a dual effect and decreased LF and CAS, while increasing TPP. The serotonin synthesis inhibitor, p-chlorophenylalanine and the selective serotonin receptor (5-HT2) antagonist, ketanserin, augmented all paradigms of FIA per se and apomorphine induced augmentation of FIA. However, the other serotonin receptor antagonist used, metergoline, which blocks both 5-HT1 and 5-HT2 receptor subtypes, attenuated FIA per se but decreased only CAS in apomorphine induced increase in FIA. The data confirm the inhibitory effect of the central serotonergic system on aggressive behaviour and the inverse relationship existing between it and the central dopaminergic system in the modulation of FIA, as has also been confirmed in earlier biochemical investigations from this laboratory. The data has been discussed in the light of existing knowledge on serotonin receptor subtypes and the presence of modulatory serotonergic heteroreceptors on central dopaminergic neurones.