Methimazole-induced hypothyroidism inhibits the panic-like behaviors produced by electrical stimulation of dorsal periaqueductal gray matter of rats

• Published in: Psychoneuroendocrinology 2010-06, Vol.35 (5), p.706-716
• Main Authors: Siqueira, Carla Coelho, Rossoni, Renzo Roldi, Tiengo, Ana Neide Carleti Pereira, Tufik, Sérgio, Schenberg, Luiz Carlos
• Format: Article
• Language: English
• Subjects: Adult and adolescent clinical studies; Animals; Anxiety; Anxiety - drug therapy; Anxiety disorders. Neuroses; Behavioral psychophysiology; Biological and medical sciences; Defensive behaviors; Disease Models, Animal; Electric Stimulation; Elevated plus-maze; Endocrinology & Metabolism; Endocrinopathies; Fundamental and applied biological sciences. Psychology; Hormones and behavior; Hypothyroidism - chemically induced; Male; Maze Learning - drug effects; Medical sciences; Methimazole - therapeutic use; Non tumoral diseases. Target tissue resistance. Benign neoplasms; PAG; Panic; Panic disorder; Panic Disorder - drug therapy; Periaqueductal Gray - drug effects; Periaqueductal Gray - physiology; Psychiatry; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Psychopathology. Psychiatry; Rats; Rats, Wistar; Thyroid; Thyroid. Thyroid axis (diseases); Thyrotropin - blood; Thyroxine - blood
• ISSN: 0306-4530; 1873-3360
• DOI: 10.1016/j.psyneuen.2009.10.011

Summary 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 μA 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 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.