The serotonin 1A receptor (or 5-HT1A receptor) is a subtype of serotonin receptor (5-HT receptor) that binds the neurotransmitter serotonin (5-hydroxytryptamine. 5-HT1A receptors in clinical psychopharmacology: neuropharmacology, their role in anxiety, depression and schizophrenia. List of approved partial agonists. In this review, we examine the function of 5-HT1A receptor sub-populations and re-interpret our understanding of their role in mental illness in.
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Can we really accelerate and enhance the selective serotonin reuptake inhibitor antidepressant effect?. A randomized clinical trial and a meta-analysis of pindolol in nonresistant depression. Epub Oct The depressive-like behaviors are correlated with decreased phosphorylation of mitogen-activated protein kinases in rat brain following chronic forced swim stress. Fluoxetine increases the activity of the ERK-CREB signal system and alleviates the depressive-like behavior in rats exposed to chronic forced swim stress.
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Archived from the original on Pharmacology Biochemistry and Behavior. Lesch KP, Gutknecht L Kalipatnapu S, Chattopadhyay A Regulation of cyclic AMP levels and T cell proliferation by 5-hydroxytryptamine".
Parks CL, Shenk T Retrieved 11 April Cell surface Intracellular Co-receptor. Signal transducing adaptor protein Scaffold protein. Intracrine action Neurocrine signaling Synaptic transmission Chemical synapse Neuroendocrine signaling Exocrine signalling Pheromones Mechanotransduction Phototransduction Ion channel gating Gap junction.
GPR 1 3 4 6 12 15 17 18 19 20 21 22 23 25 26 27 31 32 33 34 35 37 39 42 44 45 50 52 55 61 62 63 65 68 75 77 78 81 82 83 84 85 87 88 92 A B B GPR 56 64 97 98 AR-A Beta blockers e. Agomelatine Atypical antipsychotics e.
With this aim, the effect of either a selective 5-HT 1A receptor antagonist WAY; N [4- 2-methoxyphenylpiperazinyl]ethyl]- N pyridinylcyclohexane carboxamide or a selective 5-HT 1A receptor agonist 8-OH-DPAT; 8-hydroxy di- n -propylamine tetralin hydrobromide was investigated in mice in combination with venlafaxine by means of the forced swimming test, a paradigm aimed at screening potential antidepressants, and the hot-plate test, a phasic pain model.
Surprisingly, the results showed that WAY produced a large decrease in the antidepressant-like effect of venlafaxine, while 8-OH-DPAT rendered effective a non-effective dose of this antidepressant.
These findings show that 5-HT 1A receptors play differing roles in modulating the antidepressant-like and antinociceptive effects of venlafaxine in the models investigated. The results imply that blockade of the 5-HT 1A receptors in the forebrain will counteract the favourable antidepressant-like effect at raphe nuclei level, and consequently, the overall effect evidenced is an antagonism.
This suggests a predominant role of 5-HT 1A receptors located in the forebrain area for the antidepressant-like effect.
In contrast, the antinociceptive effect of venlafaxine is probably potentiated due to the blockade of somatodendritic 5-HT 1A receptors in the same raphe nuclei, facilitating the descending monoaminergic pain control system. Pain is one of the most prevalent physical symptoms in depression, which makes the treatment and the prognosis of the illness difficult Greden, Antidepressants are the first-line drugs for the treatment of depression, but they are also among the first choices for the treatment of some painful conditions.
Specifically, evidence exists that dual antidepressants [serotonin 5-HT and noradrenaline NA reuptake inhibitors] have greater efficacy than selective ones for pain relief, with the older tricyclics still being the first choice Eschalier et al. Recently, a number of controlled trials with the new dual class of antidepressants venlafaxine, duloxetine and milnacipran suggest that these compounds could have a therapeutic analgesic potential Briley, ; Saarto and Wiffen, ; Urquhart et al. In the case of venlafaxine, it has been shown to be effective in relieving pain of several aetiologies such as diabetic neuropathy, migraine and fibromyalgia Ozyalcin et al.
In spite of these favourable clinical perspectives its analgesic mechanism of action remains elusive. Based on reports of the known comorbidity between chronic pain and depressive illness, it is possible that these disease states are linked, i. In particular, it has been suggested that 5-HT 1A receptors play a role in the regulation of cognitive, emotional, and pain states due to their elevated presence in specific brain areas, such as the raphe nuclei, cerebral cortex, limbic system, hypothalamus and spinal cord.
In the raphe nuclei they function as somatodendritic autoreceptors, controlling 5-HT release and can be activated with an acute injection of an inhibitor of 5-HT reuptake, such as venlafaxine, limiting the increase in extracellular 5-HT in projection areas such as the forebrain Bortolozzi et al. Consequently, antidepressants' greater or lesser degree of clinical effectiveness has been related to the blockade of 5-HT 1A receptor activity in the raphe nuclei Adell et al.
A similar mechanism, which involves the raphe spinal pathway descending monoaminergic pain control system , has been suggested for 5-HT 1A autoreceptors in analgesia Mico et al. In forebrain areas, the activation of post-synaptic 5-HT 1A receptors has been related to the antidepressant effect of tricyclic antidepressants, selective serotonin reuptake inhibitors SSRIs , venlafaxine and electroconvulsive shock treatment Beique et al.
Moreover, in the spinal cord, the activation of 5-HT 1A receptors has been related to both pro- and antinociceptive effects Millan, Considering these findings, different pharmacological consequences may be triggered by either the activation or antagonism of different 5-HT 1A receptor populations, this being of particular interest in the coexistence and treatment of pain and depression.
From a preclinical point of view, conflicting data exist with respect to the effect of the modulation of 5-HT 1A receptors on the action of antidepressants. For instance, in the forced swimming test FST , one of the most used tests to detect antidepressant-like activity, the blockade of 5-HT 1A receptors enhanced the antidepressant-like activity of the selective and dual reuptake inhibitors Millan et al.
These differing effects have also been reported in patients with clinical depression. In this sense, it has been demonstrated recently that pindolol a partial 5-HT 1A receptor antagonist accelerates the antidepressant response but does not increase the effectiveness of SSRIs in unresponsive patients for review see Artigas et al.
In rats, different dosage ranges or experimental procedures might account for these differences. Regarding pain models, we and others have demonstrated an augmentation of the antinociceptive effect of different compounds with antidepressant-like effects when they are combined with 5-HT 1A antagonists Ardid et al.
Unfortunately, at the present time no clinical data have been reported regarding this approach in humans with chronic pain. Taking into account that depression and pain are two entities which are sometimes interrelated and that venlafaxine has antidepressant and analgesic effects, and in view of the importance of 5-HT 1A receptors in modulating both states, the aim of the present study has been to investigate the role these receptors play in the modulation of these functions in the effect of venlafaxine.
Experiments were performed using male albino CD1 mice 25—30 g. Animals were maintained under standard conditions: Animals were housed in groups of 10, and a 7-d acclimatization period was allowed before the experiments began. All mice were experimentally naive and used only once and 9—10 subjects were used per group. The experiments were performed during the light phase between The following drugs were used in the study: All drugs were freshly prepared immediately prior to use.
They were dissolved in physiological saline 0. Control animals received saline only. The treatments were administered under blind conditions. The FST was used to determine the role of 5-HT 1A receptors in the antidepressant-like effect of venlafaxine, following the classic method described by Porsolt et al. Tests were video-recorded and subsequently a highly trained observer, who was unaware of the treatment, evaluated the duration of immobility during the last 4 min of the 6-min testing period.
A mouse was judged to be immobile when it remained floating in the water making only the movements necessary to keep its head above the water. Reduction of immobility in this test was considered to indicate antidepressant activity. The hot-plate test was used as a phasic pain model in order to evaluate the role of 5-HT 1A receptors in the antinociceptive effect of venlafaxine.
Animals were treated under the same conditions as for antidepressant testing. Latency was considered as the time in seconds between when the animal was placed on the hot-plate surface and when it either licked or shook its hind paw or jumped. These responses are considered to be supraspinally integrated Le Bars et al. Basal latency was determined as the mean of two trials with a delay of 30 min between each one in order to randomize animal groups.
After this, test latency was determined after drug injection. A cut-off time was established at 60 s in order to avoid tissue damage to the animal. The activity was monitored for 10 min. First, dose—response relationships were established for venlafaxine in the FST 2. Second, the role of blockade of 5-HT 1A receptors on both the antidepressant-like and antinociceptive effects was studied. Fourth, locomotor activity was assessed in order to explore the possible role of motor activity in the results obtained in the FST and hot-plate test.
In the FST, the antidepressant-like effect was evaluated and expressed as immobility time in seconds. Locomotor activity was expressed as the mean activity counted arbitrary units. In the hot-plate test, the level of analgesia was expressed as latency time in seconds. The effects of venlafaxine compared to the saline group were established by a one-way analysis of variance ANOVA followed by Dunnett's test.
The factors of variation were venlafaxine treatment and 5-HT 1A receptor antagonist or agonist treatment.
5-HT1A receptors in depression – getting to the hub of the matter
One target that might help antidepressant drugs work faster is one of the many receptors for serotonin, the 5-HT1A receptor. Receptors are. The 5-HT1A receptor is an inhibitory G-protein-coupled receptor found in the region of origin of 5-HT projections in the CNS, the raphe nuclei of the brainstem. The Serotonin 5HT1A receptor is more important than you think. Even if you don't have your genetic data from 23andme, you should still read.