TY - JOUR
T1 - Pharmacological modulation of abnormal involuntary DOI-induced head twitch response in male DBA/2J mice
T2 - I. Effects of D2/D3 and D2 dopamine receptor selective compounds
AU - Rangel-Barajas, Claudia
AU - Malik, Maninder
AU - Vangveravong, Suwanna
AU - Mach, Robert H.
AU - Luedtke, Robert R.
N1 - Funding Information:
This work was supported in part by NIH/NIMH : R21/R33 NS050658-01A1 . The authors would like to thank Ms. Michelle Taylor and Ms. Suzy Griffin for their assistance with the preparation of this manuscript. We would also like to thank Drs. William P. Clarke and Kelly A. Berg in the Department of Pharmacology at the University of Texas Health Science Center at San Antonio for providing us with the transfected cell lines expressing 5-HT2a and 5-HT2c receptors and for providing us with information about the radioligand binding protocols.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2014/8
Y1 - 2014/8
N2 - 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.
AB - 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.
KW - 5-HT2 serotonin receptor agonist
KW - Antipsychotics and psychiatric disorders
KW - D2 dopamine receptors
KW - DOI
KW - Head twitch response
UR - http://www.scopus.com/inward/record.url?scp=84898787811&partnerID=8YFLogxK
U2 - 10.1016/j.neuropharm.2014.03.003
DO - 10.1016/j.neuropharm.2014.03.003
M3 - Article
C2 - 24680675
AN - SCOPUS:84898787811
SN - 0028-3908
VL - 83
SP - 18
EP - 27
JO - Neuropharmacology
JF - Neuropharmacology
ER -