Attenuation of the effect of punishment by thyrotropin releasing hormone: Comparisons with chlordiazepoxide

Thyrotropin releasing hormone (TRH), like chlordiazepoxide, significantly attenuated the suppressive effect of punishment on licking behavior in water deprived rats. Following i.p. administration of TRH (40 mg/kg), greatest effects were observed between 15 to 60 min, indicating that this action did not closely parallel TRH induced piloerection and tremor. Intracisternal administration of TRH at doses as low as 1 μg/brain increased punished responding and elevated serum thyrotropin (TSH), but not prolactin. However, neither systemically administered TSH, which resulted in serum thyrotropin concentrations greater than those observed after TRH administration, nor a large dose of triiodothyronine, affected punished responding. These latter results suggest that TRH is not acting through the pituitary thyroid axis to produce effects on punished behavior. MK-771, an analog of TRH active in other paradigms, similarly increased punished responding after both i.p. and intracisternal administration. Neither TRH free acid (inactive in other paradigms) nor Pro-Leu-Gly-NH ₂ (MIF) altered this behavior. Additionally, it was demonstrated that TRH at a dose which produced a significant change in punished responding did not affect unpunished drinking or jump flinch thresholds to aversive shock administration, suggesting that the action of TRH on punished responding did not result from alterations in either thirst motivation or sensitivity to aversive stimulation. Whereas d-amphetamine was equally potent in antagonizing the effect of TRH or chlordiazepoxide (CDZ) on punished responding, several findings contrasted the actions of these drugs. TRH elevated serum TSH and corticosterone as well as cerebellar cyclic guanosine 3':5' monophosphate (cGMP), whereas CDZ did not alter TSH and reduced both serum corticosterone and cerebellar cGMP content. Specific binding of [ ³H]flunitrazepam to cortical membranes was decreased by CDZ but not by TRH. Finally, naloxone was a more potent antagonist of the antipunishment effects of TRH than it was of CDZ. These results suggest that although TRH and CDZ similarly altered punished behavior, there may be differences in their mode of action.