Prenatal exposure to morphine or naloxone intensifies morphine dependence at maturity

Pregnant rats were SC injected with physiological saline (control) or 10 mg/kg morphine (morphine group) or 2 mg/kg naloxone (naloxone group) three times daily during the last 5 days of gestation. Three weeks after birth, male young rats of each group were taken and placed in separate cages. When their body weight reached 130-150 g, 10 rats from control, morphine, and naloxone groups were SC implanted with two pellets containing 75 mg morphine base (total 150 mg). Three days following implantation, rats were IP given 2 mg/kg naloxone for precipitated abstinence syndrome. Immediately after naloxone injection, rats were strictly observed for 15 min and jumping, wet-dog shakes, teeth-chattering, diarrhoea, defecation, and ptosis counted or rated. All abstinence syndrome signs were significantly higher in the morphine or naloxone group than in control. On the basis of the previous experimental findings supporting the idea that opiate physical dependence is related to the binding of opiate, possibly other than their own, to NMDA receptors and the upregulation and/or supersensitivity associated with the binding, the intensification of morphine dependence has been attributed to the long-lasting NMDA receptor upregulation and/or supersensitivity.