Effect of thyrotropin-releasing hormone on the locomotor and sensitizing effects of cocaine in rats

Abstract

The present study was designed to find out whether single and repeated treatment with thyrotropin-releasing hormone (TRH) changed the cocaine-evoked hyperactivation or sensitization, and whether cross-sensitization occurred between TRH and cocaine. Like cocaine (10 mg/kg), TRH (10 mg/kg) increased the basal activation of rats; however, when given in combination with cocaine (10 mg/kg), TRH (5–10 mg/kg) did not change the locomotor effect of cocaine. On day 10, cocaine challenge of rats treated repeatedly with the psychostimulant (days 1–5) significantly enhanced locomotor hyperactivity compared to the effect of acute cocaine injection in saline-treated (days 1–5) animals. When co-administered with cocaine for 5 days during the development of sensitization, TRH (10 mg/kg) enhanced the effect of the challenge dose of cocaine (10 mg/kg) following a 5-day withdrawal. Given acutely with cocaine on day 10 to cocaine-treated animals, TRH (5–10 mg/kg) did not change the expression of cocaine sensitization. Significant enhancement of the locomotor response to TRH (10 mg/kg) challenge was observed in animals treated repeatedly with TRH. The response to TRH (5–10 mg/kg) was stronger in repeated cocaine-treated rats than in saline-injected ones; similarly, the response to cocaine (10 mg/kg) was more potent in TRH-treated animals compared to saline-injected ones (cross-sensitization). In conclusion, our results indicate that exposure to TRH induces sensitization to its locomotor hyperactivity effect. They also show that TRH enhances the development of cocaine sensitization, but affects neither the expression phase of the phenomenon nor the locomotor hyperactivity induced by a single dose of cocaine. Moreover, cross-sensitization between cocaine and TRH has also been demonstrated. These findings also may provide an insight into the relationship between TRH and cocaine in humans exposed to the psychostimulant.