title: Pharmacological modulation of abnormal involuntary DOI-induced head twitch response in male DBA/2J mice: I. Effects of D2/D3 and D2 dopamine receptor selective compounds.
abstract: Because of the complexity and heterogeneity of human neuropsychiatric disorders, it has been difficult to identify animal models that mimic the symptoms of these neuropathologies and can be used to screen for antipsychotic agents. For this study we selected the murine 5HT2A/2C receptor agonist-induced head twitch response (HTR) induced by the administration of 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), which has been proposed as an animal model of symptoms associated with a variety of behavioral and psychiatric conditions. We investigated the DOI-induced HTR in male DBA/2J mice using a panel of D2-like (D2, D3 and D4) and D2 dopamine receptor selective compounds. When DBA/2J mice were administered a daily dose of DOI (5 mg/kg), tolerance to the DOI occurs. However, administrations of the same dose of DOI every other day (48 h) or on a weekly basis did not lead to tolerance and the ability to induce tolerance after daily administration of DOI remains intact after repeated weekly administration of DOI. Subsequently, a panel of D2-like dopamine receptor antagonists was found to effectively inhibit the DOI-induced HTR in DBA/2J mice. However, the benzamide eticlopride, which is a high affinity D2-like antagonist, was a notable exception. SV 293, SV-III-130s and N-methylbenperidol, which exhibit a high affinity for D2 versus the D3 dopamine receptor subtypes (60- to 100-fold binding selectivity), were also found to inhibit the HTR in DBA/2J mice. This observation suggests a functional interaction between dopaminergic and serotonergic systems through D2 dopamine receptors and the 5-HT2A serotonin receptors in vivo.
authors.affiliation: University of North Texas Health Science Center, the Department of Pharmacology and Neuroscience, 3500 Camp Bowie Boulevard, Fort Worth, TX 76107, USA.
authors.forename: Claudia
authors.initials: C
authors.lastname: Rangel-Barajas
authors.affiliation: University of North Texas Health Science Center, the Department of Pharmacology and Neuroscience, 3500 Camp Bowie Boulevard, Fort Worth, TX 76107, USA.
authors.forename: Maninder
authors.initials: M
authors.lastname: Malik
authors.affiliation: Division of Radiological Sciences, Washington University School of Medicine, Mallinckrodt Institute of Radiology, 510 S. Kingshighway, St. Louis, MO 63110, USA.
authors.forename: Suwanna
authors.initials: S
authors.lastname: Vangveravong
authors.affiliation: Radiochemistry Laboratory, Neurology Department, University of Pennsylvania School of Medicine, Chemistry Building, 231 S. 34th Street, Philadelphia, PA 19104, USA.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Mach
authors.affiliation: University of North Texas Health Science Center, the Department of Pharmacology and Neuroscience, 3500 Camp Bowie Boulevard, Fort Worth, TX 76107, USA. Electronic address: rluedtke@hsc.unt.edu.
authors.forename: Robert R
authors.initials: RR
authors.lastname: Luedtke
mesh_terms: D000662:Amphetamines / Q000633:toxicity*; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D065127:Dopamine D2 Receptor Antagonists / Q000493:pharmacokinetics / Q000494:pharmacology*; D004361:Drug Tolerance; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D050637:Receptors, Dopamine D3 / Q000037:antagonists & inhibitors*; D058826:Serotonin 5-HT2 Receptor Agonists / Q000633:toxicity*
chemical_list: D000662:Amphetamines; D014150:Antipsychotic Agents; D065127:Dopamine D2 Receptor Antagonists; D050637:Receptors, Dopamine D3; D058826:Serotonin 5-HT2 Receptor Agonists; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine
keywords: 5-HT2 serotonin receptor agonist; Antipsychotics and psychiatric disorders; D2 dopamine receptors; DOI; Head twitch response