Alicja Zakrzewska-Sito1, Przemysław Bieńkowski2, Marcin Kołaczkowski3, Irena Nalepa4, Agnieszka Zelek-Molik4, Adam Bielawski4, Katarzyna Chorążka4, Julita Kuczyńska1, Paweł Mierzejewski5. 1. Department of Pharmacology, Institute of Psychiatry and Neurology, ul. Sobieskiego 9, 02-957, Warsaw, Poland. 2. Department of Psychiatry, Warsaw Medical University, Nowowiejska 27, 00-665, Warsaw, Poland. 3. Department of Medicinal Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688, Kraków, Poland. 4. Department of Brain Biochemistry, Maj Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, 31-343, Kraków, Poland. 5. Department of Pharmacology, Institute of Psychiatry and Neurology, ul. Sobieskiego 9, 02-957, Warsaw, Poland. mierzeje@ipin.edu.pl.
Abstract
RATIONALE: We have discovered that rats at the age of 18 months begin to twitch their heads spontaneously (spontaneous head twitching, SHT). To date, no one has described this phenomenon. OBJECTIVES: The purpose of this study was to characterize SHT pharmacologically and to assess some possible mechanisms underlying SHT. METHODS: Wistar male rats were used in the study. Animals at the age of 18 months were qualified as HSHT (SHT ≥ 7/10 min observations) or LSHT (SHT < 7/10 min observations). Quantitative real-time PCR with TaqMan low-density array (TLDA) approach was adopted to assess the mRNA expression of selected genes in rat's hippocampus. RESULTS: HSHT rats did not differ from LSHT rats in terms of survival time, general health and behavior, water intake, and spontaneous locomotor activity. 2,5-dimethoxy-4-iodoamphetamine (DOI) at a dose of 2.5 mg/kg increased the SHT in HSHT and LSHT rats, while ketanserin dose-dependently abolished the SHT in the HSHT rats. The SHT was reduced or abolished by olanzapine, clozapine, risperidone, and pimavanserin. All these drugs have strong 5-HT2A receptor-inhibiting properties. Haloperidol and amisulpride, as antipsychotic drugs with a mostly dopaminergic mechanism of action, did not influence SHT. Similarly, escitalopram did not affect SHT. An in-depth gene expression analysis did not reveal significant differences between the HSHT and the LSHT rats. CONCLUSIONS: SHT appears in some aging rats (about 50%) and is permanent over time and specific to individuals. The 5-HT2A receptor strongly controls SHT. HSHT animals can be a useful animal model for studying 5-HT2A receptor ligands.
RATIONALE: We have discovered that rats at the age of 18 months begin to twitch their heads spontaneously (spontaneous head twitching, SHT). To date, no one has described this phenomenon. OBJECTIVES: The purpose of this study was to characterize SHT pharmacologically and to assess some possible mechanisms underlying SHT. METHODS: Wistar male rats were used in the study. Animals at the age of 18 months were qualified as HSHT (SHT ≥ 7/10 min observations) or LSHT (SHT < 7/10 min observations). Quantitative real-time PCR with TaqMan low-density array (TLDA) approach was adopted to assess the mRNA expression of selected genes in rat's hippocampus. RESULTS: HSHT rats did not differ from LSHT rats in terms of survival time, general health and behavior, water intake, and spontaneous locomotor activity. 2,5-dimethoxy-4-iodoamphetamine (DOI) at a dose of 2.5 mg/kg increased the SHT in HSHT and LSHT rats, while ketanserin dose-dependently abolished the SHT in the HSHT rats. The SHT was reduced or abolished by olanzapine, clozapine, risperidone, and pimavanserin. All these drugs have strong 5-HT2A receptor-inhibiting properties. Haloperidol and amisulpride, as antipsychotic drugs with a mostly dopaminergic mechanism of action, did not influence SHT. Similarly, escitalopram did not affect SHT. An in-depth gene expression analysis did not reveal significant differences between the HSHT and the LSHT rats. CONCLUSIONS: SHT appears in some aging rats (about 50%) and is permanent over time and specific to individuals. The 5-HT2A receptor strongly controls SHT. HSHT animals can be a useful animal model for studying 5-HT2A receptor ligands.
Authors: Greg Allen; Holly Barnard; Roderick McColl; Andrea L Hester; Julie A Fields; Myron F Weiner; Wendy K Ringe; Anne M Lipton; Matthew Brooker; Elizabeth McDonald; Craig D Rubin; C Munro Cullum Journal: Arch Neurol Date: 2007-10