Chronic psychostimulant exposure to adult, but not periadolescent rats reduces subsequent morphine antinociception

Preweanling methylphenidate (MPH) exposure produces a long lasting enhanced sensitivity to opioids. Two important questions are whether this enhancement is specific to the age of psychostimulant exposure and the type of psychostimulant. To answer these questions periadolescent (PD 35) and adult (PD 55) rats received daily injections of saline, MPH, or methamphetamine (METH) for 10 consecutive days. Two weeks later, acute morphine antinociception was assessed on the hot plate using a cumulative dose response procedure. Following acute antinociceptive testing, morphine tolerance was induced in half the animals by administering morphine twice a day over 2 days. Rats pretreated with MPH and METH during the periadolescent period of ontogeny showed no change in acute morphine antinociception, but rats exposed to a relatively high METH dose (3 mg/kg) displayed enhanced morphine tolerance compared to saline pretreated controls. MPH and METH pretreatment during adulthood led to a reduction in morphine antinociceptive potency and an apparent reduction in morphine tolerance. When combined with our previously published findings, these data indicate that the developmental stage during which MPH and METH exposure occurs differentially alters adult morphine responsiveness. That is, psychostimulant exposure to preweanling rats enhances morphine antinociception and facilitates the development of tolerance, whereas psychostimulant exposure to adult rats reduces subsequent morphine antinociception and tolerance. These alterations indicate that it could be important for physicians to know about prior psychostimulant use when prescribing opioids for pain relief.

► The age of chronic psychostimulant administration alters the effects of morphine in adults.
► Adolescent psychostimulant administration had no effect on morphine antinociception.
► Adults psychostimulant administration reduced acute morphine antinociception and tolerance.
► These data raise concerns about long-term changes from prior psychostimulant administration.