Diazepam affects the nuclear thyroid hormone receptor density and their expression levels in adult rat brain.
Thyroid hormones (THs) are involved in the occurrence of anxiety and affective disorders; however, the effects following an anxiolytic benzodiazepine treatment, such as diazepam administration, on the mechanism of action of thyroid hormones has not yet been investigated. The effect of diazepam on the in vitro nuclear T3 binding, on the relative expression of the TH receptors (TRs) and on the synaptosomal TH availability were examined in adult rat cerebral hemispheres 24 h after a single intraperitoneal dose (5 mg/kg BW) of this tranquillizer. Although, diazepam did not affect the availability of TH either in blood circulation or in the synaptosomal fraction, it decreased (33%) the nuclear T3 maximal binding density (B(max)). No differences were observed in the equilibrium dissociation constant (K(d)). The TRalpha2 variant (non-T3-binding) mRNA levels were increased by 33%, whereas no changes in the relative expression of the T3-binding isoforms of TRs (TRalpha1, TRbeta1) were observed. This study shows that a single intraperitoneal injection of diazepam affects within 24 h, the density of the nuclear TRs and their expression pattern. The latest effect occurs in an isoform-specific manner involving specifically the TRalpha2 mRNA levels in adult rat brain.
Constantinou
Caterina
C
Laboratory of Human and Animal Physiology, Department of Biology, University of Patras, Patras 265 00, Greece.
Bolaris
Stamatis
S
Valcana
Theony
T
Margarity
Marigoula
M
D000704:Analysis of Variance; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D015152:Blotting, Northern / Q000379:methods; D001921:Brain / Q000166:cytology / Q000187:drug effects*; D003975:Diazepam / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects*; D066298:In Vitro Techniques; D007456:Iodine Isotopes / Q000493:pharmacokinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D020033:Protein Isoforms / Q000378:metabolism; D051381:Rats; D011988:Receptors, Thyroid Hormone / Q000235:genetics / Q000378:metabolism*; D013574:Synaptosomes / Q000187:drug effects; D013963:Thyroid Hormones / Q000378:metabolism; D014284:Triiodothyronine / Q000493:pharmacokinetics
D014151:Anti-Anxiety Agents; D007456:Iodine Isotopes; D020033:Protein Isoforms; D011988:Receptors, Thyroid Hormone; D013963:Thyroid Hormones; D014284:Triiodothyronine; D003975:Diazepam