The effects of developmental cadmium exposure on morphine sensitization and challenge with selective D(1) and D(2) antagonists

The purpose of this investigation was to determine the effects of developmental (perinatal) cadmium exposure on the development and expression of behavioral sensitization to morphine. Adult female rats were maintained ad libitum on diets containing 0, 25, or 50 ppm added cadmium (administered as cadmium chloride) for 30 days prior to breeding with nonexposed males. This exposure regimen continued throughout the gestational period and for 15 days postnatally during lactation, at which time regular rat chow was provided. On postnatal day (PND) 21, male pups from the respective litters were weaned and placed on an unadulterated food supply (no added cadmium) and tap water for the remainder of the study. Beginning on PND 70, animals from each exposure condition (0, 25, 50 ppm exposure conditions) received, for 21 consecutive days, either vehicle (distilled water) or 10 mg/kg morphine sulfate injections (ip) prior to being monitored for locomotor activity during 80-min test sessions. Following this 21-day period of morphine sensitization training, dose-effect profiles were determined for each exposure condition with successive daily challenges of 0, 10, and 20 mg/kg morphine. Subsequently, different doses of the D(1) antagonist SCH 23390 (0.01, 0.056, and 0.10 mg/kg) and the D(2) antagonist eticlopride (0.01 and 0.056 mg/kg) were presented prior to administration of the training dose of morphine (10 mg/kg). The results of the investigation revealed that developmental cadmium exposure attenuated the development/expression of morphine sensitization. Furthermore, it was found that the suppressive effects of the D(2) antagonist eticlopride were decreased by early cadmium exposure.