title: Methimazole-induced hypothyroidism inhibits the panic-like behaviors produced by electrical stimulation of dorsal periaqueductal gray matter of rats.
abstract: Conflicting clinical data on the relationship of panic disorder and thyroid diseases illustrate the need for a simpler approach using animal models. Defensive behaviors evoked by electrical or chemical stimulation of dorsal periaqueductal gray matter (DPAG) have been proposed as a model of panic attack. Therefore, the present study examined the effects of the anti-thyroid agent methimazole (MTZ) either on the panic-like behaviors induced by electrical stimulation of DPAG or the anxiety-like behaviors of rats exposed to the elevated plus-maze (EPM). Male Wistar rats bearing electrodes in the DPAG were stimulated with stepwise increased currents. Rats which displayed galloping at intensities below 60muA were retested following 5- and 10-day treatments with MTZ (0.6mg/kg/day, i.p.) or 10- and 15-day washout periods. MTZ effects on EPM performance were assessed in separate groups. MTZ-treated groups were compared to saline-treated controls. In other experiments, rats were similarly treated with MTZ and the blood was collected for hormone assays. The 10-day treatment with MTZ produced marked increases in the thresholds of exophthalmus (65%), immobility (75%), trotting (63%), galloping (56%), jumping (47%), defecation (114%) and micturition (85%). Effects outlasted the drug discontinuation. In contrast, MTZ had variable effects in the EPM, significantly increasing the open-arm exploration in 5-day treated and 10-day washout groups. Biochemical data revealed a small but significant decrease (13%) in free thyroxine in MTZ-treated groups. Although not significant, thyrotrophin levels showed a 111% increase following the 10-day treatment with MTZ. Selective attenuation by MTZ of DPAG-evoked defensive behaviors supports attenuation of panic attacks in hypothyroidism.
authors.affiliation: Department of Physiological Sciences, Federal University of Espírito Santo, Vitória, ES, Brazil.
authors.forename: Carla Coelho
authors.initials: CC
authors.lastname: Siqueira
authors.forename: Renzo Roldi
authors.initials: RR
authors.lastname: Rossoni
authors.forename: Ana Neide Carleti Pereira
authors.initials: AN
authors.lastname: Tiengo
authors.forename: Sérgio
authors.initials: S
authors.lastname: Tufik
authors.forename: Luiz Carlos
authors.initials: LC
authors.lastname: Schenberg
mesh_terms: D000818:Animals; D001007:Anxiety / Q000188:drug therapy*; D004195:Disease Models, Animal; D004558:Electric Stimulation; D007037:Hypothyroidism / Q000139:chemically induced*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008713:Methimazole / Q000627:therapeutic use*; D016584:Panic Disorder / Q000188:drug therapy*; D010487:Periaqueductal Gray / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood
chemical_list: D008713:Methimazole; D013972:Thyrotropin; D013974:Thyroxine