Since the discovery of the first antipsychotic, pharmacological treatment of schizophrenia (SCZ) has primarily relied on dopamine D2 receptor antagonist. However, variability in treatment responses highlights the need for novel biomarkers and therapeutics targets. Here, we developed a dual-hit mouse model combining maternal immune activation (MIA) induced by polyinosinic-polycytidylic acid...
Abstract Background The psychedelic psilocybin has been posited as efficacious for the treatment of depression. However, the potential link between the intensity of acute psychedelic effects and long-term therapeutic outcomes remains undiscovered. Moreover, the impact of classical antidepressant drugs that modulate serotonergic activity on psilocybin’s effects is a clinically relevant concern....
In the rapidly growing field of psychedelic research, psilocybin (and active metabolite psilocin) has been proposed as a promising candidate in the search for novel treatments for neuropsychiatric disorders. Clinical trials have revealed that psilocybin has a large, rapid, and persistent effect in the improvement of symptoms of depression and anxiety. The safety profile is considered...
Long-term exposure to stress is associated to HPA axis alterations and the development of depression. Chronic unpredictable mild stress (CUMS) is a widely used and validated animal model of depression, and presents phenotypic features of this disease, like anhedonia and despair, along with physiological and neurochemical alterations. Recently, the psychedelic 5-HT2A agonist psilocybin has...
The psychedelic 5-HT2A receptor (5HT2AR) agonist psilocybin (or the active metabolite psilocin) has emerged as potential useful drug for various neuropsychiatric diseases, with a rapid onset of therapeutic activity. However, the mechanisms responsible for such effects remain incompletely characterized. We aimed to study in vitro pharmacological profile and in vivo acute mechanism of...
Abstract The status of serotonin 5HT 2A receptors (5HT 2A Rs) in schizophrenia has been controversial. In vivo positron emission tomography neuroimaging and in vitro post-mortem binding studies have reported conflicting results about 5HT 2A R density. Radiotracers bind different receptor conformations depending on their agonist, antagonist or inverse agonist properties. This study...
Long-term use of potent cannabis during adolescence increases the risk of developing schizophrenia later in life, but to date, the mechanisms involved remain unknown. Several findings suggest that the functional selectivity of serotonin 2A receptor (5-HT2AR) through inhibitory G-proteins is involved in the molecular mechanisms responsible for psychotic symptoms. Moreover, this receptor is...