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

Summary 

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 60μA were injected with 1μg/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 χ² 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.

Keywords: TRH, Thyroid, PAG, Flight, Freezing, Anxiety, Elevated plus-maze, Rat