Imperial College London

Dipl. Psych. Tobias Buchborn

Faculty of MedicineDepartment of Brain Sciences

Honorary Research Fellow
 
 
 
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Contact

 

+44 (0)20 7594 3205t.buchborn

 
 
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Location

 

Burlington DanesHammersmith Campus

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Summary

 

Publications

Publication Type
Year
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6 results found

Buchborn T, Lyons T, Knopfel T, 2018, Tolerance and Tachyphylaxis to Head Twitches Induced by the 5-HT2A Agonist 25CN-NBOH in Mice, Frontiers in Pharmacology, Vol: 9, ISSN: 1663-9812

The serotonin (5-HT) 2A receptor is the primary molecular target of serotonergic hallucinogens, which trigger large-scale perturbations of the cortex. Our understanding of how 5-HT2A activation may cause the effects of hallucinogens has been hampered by the receptor unselectivity of most of the drugs of this class. Here we used 25CN-NBOH (N-(2-hydroxybenzyl)-2,5-dimethoxy-4-cyanophenylethylamine), a newly developed selective 5-HT2A agonist, and tested it with regard to the head-twitch-response (HTR) model of 5-HT2A activity and effects on locomotion. 25CN-NBOH evoked HTRs with an inverted u-shape-like dose-response curve and highest efficacy at 1.5 mg/kg, i.p. HTR occurrence peaked within 5 min after agonist injection, and exponentially decreased to half-maximal frequency at ~11 min. Thorough habituation to the experimental procedures (including handling, saline injection, and exposure to the observational boxes 1 day before the experiment) facilitated the animals' response to 25CN-NBOH. 25CN-NBOH (1.5 mg/kg, i.p.) induced HTRs were blocked by the 5-HT2A antagonist ketanserin (0.75 mg/kg, 30 min pre), but not by the 5-HT2C antagonist SB-242084 (0.5 mg/kg, i.p., 30 min pre). SB-242084 instead slightly increased the number of HTRs occurring at a 3.0-mg/kg dose of the agonist. Apart from HTR induction, 25CN-NBOH also modestly increased locomotor activity of the mice. Repeated once-per-day injections (1.5 mg/kg, i.p.) led to reduced occurrence of 25CN-NBOH induced HTRs. This intermediate tolerance was augmented when a second (higher) dose of the drug (3.0 mg/kg) was interspersed. Short-interval tolerance (i.e., tachyphylaxis) was observed when the drug was injected twice at intervals of 1.0 and 1.5 h at either dose tested (1.5 mg/kg and 0.75 mg/kg, respectively). Inducing ketanserin-sensitive HTRs, which are dependent on environmental valences and which show signs of tachyphylaxis and tolerance, 25CN-NBOH shares striking features common to serotonergic hallucinogens. Gi

Journal article

Buchborn T, Grecksch G, Dieterich D, Hoellt Vet al., 2016, Tolerance to Lysergic Acid Diethylamide: Overview, Correlates, and Clinical Implication, Neuropathology of Drug Addictions and Substance Misuse. Volume 2: Stimulants, Club and Dissociative Drugs, Hallucinogens, Steroids, Inhalants and International Aspects., Editors: Preedy, Pages: 846-858

The first reports on tolerance to the serotonergic hallucinogen lysergic acid diethylamide (LSD) were published half a century ago, yet hitherto, a systematic review on this topic is not available. In this chapter, we discuss tolerance to LSD with regard to its psychedelic and somatic effects in humans, as well as selected behaviors in animals. In humans, mental tolerance to LSD substantially manifests 24 h after its first administration and reaches a maximum by around the fourth day. Once established, tolerance cannot be overcome even if the initial dose is quadrupled. Mental tolerance to LSD generalizes to psilocybin and mescaline but not to tetrahydrocannabinol or amphetamine. As to LSD’s somatic effects, mental tolerance most reliably is accompanied by tolerance to mydriasis. Five days of abstinence is sufficient for tolerance to be reversed; symptoms of withdrawal are not encountered. In animals, LSD-induced shaking behavior, limb flicking, and hallucinogenic pausing are undermined by tolerance, too; the first-mentioned behaviors, for instance, are subject to tachyphylaxis. Mechanistically, pharmacodynamic adaptations of serotonin 5-HT2A and/or (downstream) glutamate receptors are likely to account for tolerance; a learning-related precipitation, however, has also been described. The rapid onset of mental tolerance probably is a main reason LSD generally is not taken on an everyday basis by humans. Given its rapid reversal, on the other hand, a once-per-week abuse cannot be excluded.

Book chapter

Buchborn T, Schroeder H, Koch T, Kahl E, Dieterich DC, Grecksch G, Hoellt Vet al., 2016, Differential tolerance to lysergic acid diethylamide (LSD) and dimethyltryptamine (DMT) - A matter of serotonin (5-HT) 2A receptor downregulation?, 82nd Annual Meeting of the German-Society-for-Exerimental-and-Clinical-Pharmacology-and-Toxicology (DGPT) / 18th Annual Meeting of the Network-Clinical-Pharmacology-Germany (VKliPha), Publisher: SPRINGER, Pages: S63-S63, ISSN: 0028-1298

Conference paper

Buchborn T, Schroeder H, Dieterich DC, Grecksch G, Hoellt Vet al., 2015, Tolerance to LSD and DOB induced shaking behaviour: Differential adaptations of frontocortical 5-HT2A and glutamate receptor binding sites, BEHAVIOURAL BRAIN RESEARCH, Vol: 281, Pages: 62-68, ISSN: 0166-4328

Journal article

Buchborn T, Schroeder H, Hoellt V, Grecksch Get al., 2014, Repeated lysergic acid diethylamide in an animal model of depression: Normalisation of learning behaviour and hippocampal serotonin 5-HT2 signalling, JOURNAL OF PSYCHOPHARMACOLOGY, Vol: 28, Pages: 545-552, ISSN: 0269-8811

Journal article

Buchborn T, Kahl E, Hoellt V, Koch Tet al., 2012, Agonist-selective internalization of the human 5-HT2A receptor, 78th Annual Congress of the German-Society-for-Experimental-and-Clinical-Pharmacology-and-Toxicology (DGPT), Publisher: SPRINGER, Pages: 17-17, ISSN: 0028-1298

Conference paper

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