Methimazole-induced hypothyroidism inhibits the panic-like behaviors produced by electrical stimulation of dorsal periaqueductal gray matter of rats.
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.
Siqueira
Carla Coelho
CC
Department of Physiological Sciences, Federal University of Espírito Santo, Vitória, ES, Brazil.
Rossoni
Renzo Roldi
RR
Tiengo
Ana Neide Carleti Pereira
AN
Tufik
Sérgio
S
Schenberg
Luiz Carlos
LC
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
D008713:Methimazole; D013972:Thyrotropin; D013974:Thyroxine