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.

Dorsal periaqueductal gray matter-evoked panic-like behaviors are markedly inhibited by a low peripheral dose of thyrotropin releasing hormone.

Stimulation of the dorsal periaqueductal gray matter (DPAG) produces defensive behaviors which are reminiscent of panic attacks. Recent evidence from our laboratory showed that DPAG-evoked defensive behaviors are markedly attenuated in short-term methimazole-induced hypothyroidism. It is not clear, however, whether these effects were due to an increase in thyrotropin releasing hormone (TRH), a decrease in thyroid hormones or to the overall effects of hypothyroidism. Accordingly, here we examined whether the peripheral injection of TRH has any effect either on the panic-like behaviors induced by electrical stimulation of DPAG or anxiety-like behaviors of rats exposed to the elevated plus-maze (EPM). Rats whose stimulation of DPAG produced flight responses (galloping or jumping) with intensities below 60 microA were injected with 1 microg/kg TRH (i.p.) and stimulated 10min after that. The day after, rats were treated with saline and subjected to the same stimulation procedure. Threshold curves were fitted through the logistic model and compared by likelihood-ratio chi(2) tests. TRH and saline effects on EPM performance were appraised in separate groups. Compared to saline-sessions, TRH-injected rats presented thresholds significantly higher for immobility (40%), trotting (33%), galloping (34%), jumping (39%) and exophthalmus (43%). In contrast, TRH had no effects on EPM arm exploration. TRH selective inhibition of DPAG-evoked defensive behaviors adds new evidence that panic attacks may be attenuated by increased levels of this hormone in hypothyroidism.

Sindrome plurimetabólica / Metabolic syndrome

A síndrome plurimetabólica é definida por um conjunto de anormalidades metabólicas, caracterizada por resistência celular à açäo periférica da insulina, hiperinsulinemia compensatória, hipertensäo, obesidade intra-abdominal (visceral), dislipidemia caracterizada por níveis séricos diminuídos de lipoproteína de alta densidade (HDL) e elevados de lipoproteína de baixa densidade(LDL) e de muito baixa densidade(VLDL), além de um risco aumentado no desenvolvimento de doenças cardiovasculares e diabetes mellitus tipo 2. Também podem ser observados nos pacientes: alteraçöes na coagulaçäo sangüínea, hiperuricemia, hiperfibrogenemia, microalbuminúria, maior incidência de ovários policisticos, apnéia do sono, depressäo e alguns tumores. O tratamento consiste em medidas näo farmacológicas(dietas especiais e exercícios físicos) e farmacológicas(tiazolidinedionas, biguanidas, inibidores da ECA e bloqueadores de receptores AT1, além do emprego de outros agentes anti-hipertensivos). Este artigo faz uma revisäo sobre os principais aspectos da epidemiologia, patogênese, clínica, formas de tratamento e prevençäo da síndrome plurimetabólica.(au)