Discriminative stimulus properties of the 5-HT(1A) receptor biased agonists NLX-101 and F13714, in rats trained to discriminate 8-OH-DPAT from saline
| Autor: | Jillian Helen Broadbear, Brendan J. Tunstall, Kristina Vacy, Ronan Depoortère, David Ralph, Adrian Newman-Tancredi |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Agonist
Male medicine.drug_class Pyridines Aminopyridines Pharmacology Partial agonist Article Piperazines Buspirone Discrimination Learning Rats Sprague-Dawley chemistry.chemical_compound Piperidines polycyclic compounds medicine Animals heterocyclic compounds Receptor 8-Hydroxy-2-(di-n-propylamino)tetralin Dose-Response Relationship Drug Chemistry 8-OH-DPAT musculoskeletal neural and ocular physiology Serotonin 5-HT1 Receptor Agonists Receptor antagonist Rats Psychiatry and Mental health Pyrimidines nervous system 5-HT1A receptor Female Serotonin medicine.drug |
| Zdroj: | Behav Pharmacol |
| Popis: | NLX-101 and F13714 are selective, full efficacy, biased agonists of the 5-HT(1A) receptor. NLX-101 preferentially activates cortical post-synaptic 5-HT(1A) receptors whereas F13714 preferentially activates Raphe nuclei pre-synaptic 5-HT(1A) receptors. We compared NLX-101 and F13714 for their efficacy and potency to substitute for the discriminative cue produced by the prototypical, non-biased 5-HT(1A) receptor agonist, 8-OH-DPAT (racemate). Male and female Sprague-Dawley rats were trained to discriminate 8-OH-DPAT (0.1 mg/kg i.p., 20 min pre-treatment) from saline using a classical two-lever drug-discrimination procedure. 8-OH-DPAT (0.01 and 0.05 mg/kg i.p.) dose-dependently substituted for the training dose, with about 50 % responding on the 8-OH-DPAT-associated lever at 0.05 mg/kg. F13714 fully and very potently substituted for the training dose of 8-OH-DPAT from 0.018 mg/kg i.p., while NLX-101 only achieved full substitution at 0.5 mg/kg i.p., a dose which is known to also activate pre-synaptic 5-HT(1A) receptors. The 5-HT(1A) receptor partial agonist, buspirone, partially substituted (~80%) at 1 and 2 mg/kg i.p., doses which also decreased response rates. F13714 decreased response rates at 0.05 mg/kg. The selective 5-HT(1A) receptor antagonist WAY-100,635 (1 mg/kg s.c., 40 min pre-treatment) elicited almost no responding on the 8-OH-DPAT-associated lever by itself, but blocked the discriminative stimulus effects produced by administration (20 min pretreatment) of 8-OH-DPAT (0.1 mg/kg), F13714 (0.025 mg/kg), NLX-101 (0.5 mg/kg), or buspirone (1 mg/kg). These data suggest that the discriminative cue produced by 0.1 mg/kg i.p. 8-OH-DPAT results from activation of pre-synaptic 5-HT(1A) receptors. They also further demonstrate the distinct profiles in behavioral models of 5-HT(1A) receptor biased agonists. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|