*Corresponding author email: Michel.bourin@univ-nantes.fr Symbiosis Group Symbiosis www.symbiosisonline.org www.symbiosisonlinepublishing.com SOJ Pharmacy & Pharmaceutical Sciences Open Access Review article Are Antidepressants Mood Agents Or Anxiolytic Drugs? Michel Bourin* Neurobiology of anxiety and mood disorders, University of Nantes, France Received: May 23, 2018; Accepted: June 29, 2018; Published: July 05, 2018 *Corresponding author: Michel Bourin, Neurobiology of anxiety and mood disorders, University of Nantes, France, Email: Michel.bourin@univ-nantes.fr Abstract Many advances have been made in the treatment of depression with the recent discovery of selective serotonin reuptake inhibitors (SSRIs) and mixed serotonin and norepinephrine reuptake inhibitors (SNRIs). Behavioral, electrophysiology, and microdialysis studies have shown that serotonin receptors, mainly the 5-HT1A, 5-HT1B, and 5-HT2C subtypes, play a key role in modulating antidepressant activity. The indirect activation of serotonergic receptors by antidepressants could lead, via an increase in 5-HT concentrations in the synapse of certain brain regions, to the activation of G proteins which would cascade the transcription of neurotrophic factor such as “the brain- derived neurotrophic factor “(BDNF). Depression could be considered as an anomaly of transduction mechanisms, this hypothesis needs to be deepened by molecular biology studies. The fact that antidepressants are also active in the treatment of anxiety disorders, questions about the nature of their mechanism in these various pathologies. Key words: Antidepressants; Serotonin Receptors; Mood Disorders; Anxiety Disorder Introduction Although several hypotheses have been put forward, the aetiology of depression is still poorly defined. The first major theory of depression, i.e., the monoaminergic theory, proposes that this disorder is due in particular to a deficiency of serotonin (5-HT) and norepinephrine (NA) [1, 2, 3, and 4]. Moreover, some molecules that deplete these neurotransmitters, such as reserpine, can induce a depressive state in a small percentage of individuals. However, this simplistic theory cannot explain the pathophysiology of depression by itself since the efficacy of antidepressants is observed clinically after a few weeks of treatment. A second hypothesis based on neurotransmitter receptors has been issued. According to this hypothesis, the depression is due to an abnormal functioning of the monoamine receptors. This receptor disruption could itself be caused by depletion of monoaminergic neurotransmitters. Advances in molecular and cellular biology suggest the role of neurotrophic factors, such as the “brain-derived neurotrophic factor” (BDNF) suggesting a neurodegenerative hypothesis to the pathophysiology of depression [4, 5]. In addition, antidepressants are now widely used in the treatment of anxiety disorders, whether generalized anxiety, panic disorder, social anxiety and post-traumatic stress, which makes it possible to wonder about the different nature of their mechanism of action. Targets for action of antidepressants Serotoninergic receptors Role of 5-HT1A receptors on antidepressant activity Various behavioral, electrophysiological and microdialysis studies have highlighted the role of 5-HT1A receptors in the pharmacological properties of antidepressants. Thus, the effects of the administration of a single dose of antidepressant on an animal model of desperation (forced swimming test) carried out in mice, suggests that the action of imipramine is via the 5-HT1A postsynaptic receptors [6]. Blier and de Montigny [7] in electrophysiology studies have shown that chronic treatment with a selective serotonin reuptake inhibitor (SSRI) induces functional desensitization of 5-HT1A autoreceptors in nuclei of the dorsal raphe. Moreover, although no down-regulation of 5-HT1A autoreceptors in dorsal raphe nuclei has been observed in binding studies [8], microdialysis studies have been conducted [9, 10]. have shown that chronic treatment with SSRIs causes hypofunction of 5-HT1A autoreceptors. In contrast, postsynaptic 5-HT1A receptors do not react in the same way as 5-HT1A autoreceptors to chronic treatment with SSRIs. Indeed, postsynaptic 5-HT1A receptors, located in the hippocampus, do not undergo desensitization or “down regulation”. The 5-HT1A autoreceptors appear to be a brake on the rapidity of action of antidepressants. Indeed, during the first days of treatment the excess of NA and especially 5-HT intrasynaptic will activate autoreceivers [11]. This phenomenon called negative feedback will slow the system back. Also, a more current research pathway tries to include in the same molecule properties that would increase the speed of action of antidepressants, this would be the case of the blocking of presynaptic 5-HT1A receptors by the (-) pindolol (molecule having antagonistic properties at alpha-adrenergic receptors, 5-HT1A and 5-HT1B). Indeed, clinical studies show that the co-administration of (-) pindolol with an IRSS (fluoxetine or paroxetine) would induce a faster mood improvement in depressed patients [12-16]. This hypothesis remains controversial and is the subject of lively debate [17-19]. Role of 5-HT1B receptors on antidepressant activity Pre-clinical studies have shown that serotonin reuptake inhibitors appear to act indirectly on 5-HT1B receptors [8]. This