THYROTROPIN-RELEASING-HORMONE IN THE MECH ANISMS OF RESISTANCE AND DEVELOPMENT OF DEPENDENCE ON MORPHINE

The influence of thyrotropin-releasing hormone (TRH) on morphine-induc ed analgesic and reinforced responses was studied in two inbred strain s of rats, Fischer-344 (F344) and Wistar Albino Glaxo/GSto (WAG). Cond itioned place preference, voluntary consumption of morphine solution a nd;analgesic action of morphine in tail immersion test were studied. T here were interstrain differences in pain sensitivity, i.e., F344 rats had longer latency of tail immersion and deeper analgesic effect of m orphine (5 mg/kg, ip) than WAG rats, TRH (1 mg/kg, ip) produced a stro nger analgesic effect in WAG rats, while F344 rats demostrated only sl ight increase in pain threshold, Administration of TRH in combination with morphine significantly stronger potentiated the effect of the lat ter in WAG than in F344 rats. F344 rats preferred morphine in the two- bottle choice test and consumed relatively larger amount of morphine s olution in the drinking paradigm than WAG rats, Morphine in the dose o f 5 mg/kg (ip) induced place preference in both rat strains, Intravent ricular administration of TRH (1 mcg) produced a slight effect of plac e preference only in F344 rats, Preceded by morphine, such injection r educed. the effect of place preference, It is suggested that WAG and F 344 rats have different sensitivity of brain structures to TRH, This i s probably determined by genetic differences in dissociation of analge sic and reinforcing effects of morphine.