Opiate effects on plasma corticosteroids: relationship to dysphoria and self-administration.

Narcotic analgesics have been shown to raise plasma corticosteroids in the rat. This effect has been interpreted as a response of the rat to the dysphoric properties of the drug. This interpretation is based on the observation that drugs such as nalorphine or cyclazocine which cause dysphoria in man elevate plasma corticosteroids in the rat at relatively low doses. Drugs like morphine or pentazocine which induce little dysphoria in man elevate plasma corticosteroids in the rat only at much larger doses. The corticosteroid-elevating effect is mediated by an opiate receptor since naloxone antagonizes the effect of morphine or the analgesic. U-50,488. Those narcotic analgesics which increased corticosteroid levels at low doses were also found to be poorly self-administered by rats. In contrast, compounds like morphine, pentazocine and the analgesic. U-49,274A, which were self-administered at high rates, elevated corticosteroids only after large doses. The relationship between the dose of a drug which causes elevations in corticosteroid levels and whether or not the drug is self-administered further supports the premise that elevated corticosteroid levels induced by analgesics is due to their dysphoric properties.