Stimulus properties of thyrotropin-releasing hormone

Male Sprague-Dawley rats were trained in a two-lever operant discrimination task using 20 mg/kg thyrotropin-releasing hormone (TRH) and saline as cues. Following completion of 40 daily training sessions, 22 of 25 subjects demonstrated a high level of discriminative responding based on the TRH and saline cues. An evaluation of the time course of TRH indicated that the stimulus properties peak between 5 and 15 min and dissipate substantially by 55–65 min. During additional testing, rats showed dose-dependent generalization between the training treatments (20 mg/kg TRH and saline) and novel doses of TRH (1, 5, 10, and 40 mg/kg). However, animals failed to show generalization between the training drug (20 mg/kg TRH) and d-amphetamine sulfate (0.8, 1.6, or 2.4 mg/kg); likewise, animals trained to discriminate d-amphetamine (0.8 or 1.6 mg/kg) from saline failed to show generalization between d-amphetamine and TRH (10, 20, or 30 mg/kg). Microgram quantities of TRH (2.5–25 g) administered into either the lateral or third ventricle elicited dose-dependent generalization to the training drug (TRH 20 mg/kg, i.p.), suggesting a CNS mechanism of action for this effect of TRH.