The Selective Serotonin2A Receptor Antagonist, MDL100,907, Elicits a Specific Interoceptive Cue in Rats

• Published in: Neuropsychopharmacology (New York, N.Y.) Vol. 26; no. 4; pp. 552 - 556
• Main Authors: Dekeyne, Anne, Iob, Loretta, Hautefaye, Patrick, Millan, Mark J
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.04.2002; Nature Publishing; Nature Publishing Group
• Subjects: 5-HT2A receptors; Antipsychotics; Biological and medical sciences; Drug discrimination; Drug dosages; Interoceptive; Laboratory animals; Ligands; LSD; Lysergic acid diethylamide; Medical sciences; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Pharmacology. Drug treatments; Psychopharmacology; Psychotropic drugs; Serotoninergic system; France; Interoceptive; Drug discrimination; 5-HT2A receptors; 5-HT2A serotonin receptor; Intraperitoneal administration; Interoception; Rat; Rodentia; Instrumental conditioning; 5-HT2 Serotonine receptor; Learning; Vertebrata; Mammalia; Acquisition process; Animal; Subcutaneous administration; Antagonist; Mechanism of action; Stimulus discrimination; Chemical stimulus
• ISSN: 0893-133X; 1740-634X
• DOI: 10.1016/S0893-133X(01)00389-X

Employing a two-lever, food-reinforced, Fixed Ratio 10 drug discrimination procedure, rats were trained to recognize the highly-selective serotonin (5-HT)2A receptor antagonist, MDL100,907 (0.16 mg/kg, i.p.). They attained criterion after a mean ± S.E.M. of 70 ± 11 sessions. MDL100,907 fully generalized with an Effective Dose (ED)50 of 0.005 mg/kg, s.c.. A further selective 5-HT2A antagonist, SR46349, similarly generalized with an ED50 of 0.04 mg/kg, s.c. In distinction, the selective 5-HT2B antagonist, SB204,741 (0.63 and 10.0 mg/kg), the 5-HT2B/2C antagonist, SB206,553 (0.16 and 2.5 mg/kg) and the selective 5-HT2C antagonists, SB242,084 (2.5 and 10.0 mg/kg,) and RS102221 (2.5 and 10.0 mg/kg), did not significantly generalize. In conclusion, selective blockade of 5-HT2A receptors by MDL100,907 elicits a discriminative stimulus in rats which appears to be specifically mediated via 5-HT2A as compared with 5-HT2B and 5-HT2C receptors.