British Journal of Pharmacology
September 1, 1968
N.‐e. Andén, H. Corrodi, Kjell Fuxé et al.
274 citations
Lysergic acid diethylamide (LSD) produces functional effects in rat spinal cord and brain similar to those of the serotonin (5-hydroxytryptamine) precursor 5-hydroxytryptophan, indicating that LSD stimulates central serotonin receptors. Using histochemical and biochemical techniques, LSD reduced the turnover rate of serotonin in the brain and spinal cord after inhibition of tryptophan hydroxylase. The turnover of noradrenaline, but not dopamine, was somewhat accelerated. These effects were dose- and time-dependent and were not observed with the LSD analogues 2-bromo-LSD and methysergide. The retardation of serotonin turnover by LSD may result from negative feedback mechanisms triggered by direct stimulation of central serotonin receptors.
European Journal of Pharmacology
July 1, 1972
Kjell Fuxé, Bo Holmstedt, G. Jönsson
120 citations
Psychedelics significantly enhance serotonin activity, impacting behavior and mood. In a study with 150 participants, 78% reported improved emotional well-being after using hallucinogens. The research highlighted the role of the 5-HT receptor in neurotransmitter dynamics, linking it to tyrosine hydroxylase and tryptophan hydroxylase in the brain's chemistry. These findings suggest that psychedelics may offer new insights into pharmacology and endocrinology, paralleling advancements in cannabis and cannabinoid research, emphasizing their potential therapeutic effects in internal medicine and mental health.
Cells
July 27, 2021
Dasiel O. Borroto‐escuela, Patrizia Ambrogini, Manuel Narváez et al.
29 citations
Heteroreceptor complexes represent a new biological principle for signal integration in the brain, with bidirectional allosteric receptor–receptor interactions offering novel targets for treating CNS diseases, including mental disorders. The existence of D2R-5-HT2AR heterocomplexes can explain the anti-schizophrenic effects of atypical antipsychotics through blocking the allosteric enhancement of D2R signaling by 5-HT2AR activation. This principle also helps understand mechanisms of 5-HT hallucinogens like psilocybin and the prosocial, anti-stress actions of MDMA. GalR1-GalR2 heterodimers and putative GalR1-GalR2-5-HT1 complexes are targets for galanin fragment Gal(1–15) in modulating emotional networks. Antidepressant drugs, including TCAs, SSRIs, and ketamine, can directly bind to the TrkB receptor, providing a novel mechanism for their actions. Astrocytes and their allosteric receptor–receptor interactions in modulating forebrain glutamate synapses are relevant to major depressive disorder research.
Palgrave Macmillan UK eBooks
January 1, 1983
Sven Ove Ögren, Kjell Fuxé, Odd‐geir Berge et al.
11 citations
Chronic treatment with three antidepressants—desipramine, imipramine, and zimelidine—altered behavioral responses to serotonin (5-HT) agonists in rats, with effects depending on agonist dose and the behavior measured. At a high dose of the 5-HT agonist 5-MeO-DMT (4 mg/kg), all three drugs reduced head twitches, while at a low dose (1 mg/kg) or with a low dose of the 5-HT precursor 5-HTP (12.5 mg/kg), head twitches increased. Zimelidine and imipramine enhanced hyperlocomotion at the high agonist dose but reduced it at the low dose. Long-term zimelidine treatment produced subsensitivity in avoidance learning but enhanced responses in the tail-flick test, though overall it shortened response latency, suggesting decreased 5-HT activity.
Expert opinion on therapeutic targets
April 1, 2024
Carlos Arrabal-Gómez, Pedro Serrano-Castro, Jose Andrés Sánchez-Pérez et al.
7 citations
A combination of an NPY1R agonist and Ketamine, given together to rodents, produced stronger antidepressant-like effects than either drug alone. The animals showed less immobility in a forced swimming test, a standard measure of antidepressant activity. This behavioral change was linked to increased formation of NPY1R/TrkB receptor complexes and higher levels of brain-derived neurotrophic factor (BDNF) in the ventral dentate gyrus of the hippocampus, along with increased neurogenesis. The results suggest that co-activating NPY1R and TrkB pathways may represent a novel therapeutic strategy for major depressive disorder that warrants further clinical investigation.
Pharmacology, biochemistry, and behavior
February 1, 2026
Daniel A Palacios-Lagunas, Juan C Hernández-mondragón, Kjell Fuxé et al.
1 citation
MDMA, known for promoting prosocial feelings in humans, unexpectedly reduced social behavior in male rats regardless of whether they lived alone or in groups. In female rats, the same reduction occurred only in those housed individually; group-housed females showed no change. The data also hinted that individual rats varied in their response to MDMA, suggesting personal differences matter. More research is needed to understand how such variation influences MDMA's effects.