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 60 mu A were retested following 5- and 10-day treatments with MTZ (0.6 mg/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 MU 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, MU 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 MU. Selective attenuation by MU of DPAG-evoked defensive behaviors supports attenuation of panic attacks in hypothyroidism. (c) 2009 Elsevier Ltd. All rights reserved.