The effects of thyrotropin-releasing hormone on the central nervous system responses to chronic morphine administration.

The effects of thyrotropin-releasing hormone (TRH) on abrupt and naloxone-precipitated abstinence symptoms were determined in male Swiss-Webster mice rendered dependent on morphine by SC implantation of morphine pellets. Intracerebral (IC) administration of TRH inhibited the hypothermic response observed during abrupt (removal of morphine pellets) and naloxone (0.1 mg/kg SC) precipitated withdrawal. IC injection of TRH also inhibited the naloxone-precipitated withdrawal jumping response as evidenced by increases in the dose of naloxone required to elicit the response. The effects of TRH on the development of morphine dependence were also investigated. A single SC injection of TRH (4-16 mg/kg) did not modify development of morphine dependence. Administration of TRH prior to and during morphine pellet implantation inhibited the development of dependence as evidenced by inhibition in the development of abrupt and naloxone-induced withdrawal hypothermia. Even though the hypothermic response was blocked, multiple SC administration of TRH failed to modify naloxone-induced stereotyped jumping response. These studies indicate that TRH administration can modify central nervous system responses to chronic morphine treatment and that separate sites may initiate withdrawal jumping behavior and affect temperature regulation during abrupt and antagonist-induced abstinence.