Morphine release and displacement by naloxone in vivo in morphine naive and withdrawn rats

Male Long-Evans rats, implanted in the lateral cerebroventricle with chronic indwelling push-pull cannulae, were perfused (10 μl/min) for 120 min: 20 min with 1.5 × 10^-6M morphine in sterile isotonic saline containing 2.3 mM CaCl₂ (vehicle); 40 min with vehicle; 20 min with 1.5 × 10^-6M morphine; 10 min with vehicle and 30 min with 1 × 10^-6M naloxone in vehicle. These rats and drug-naive rats were implanted s.c. with 2 × 50 mg morphine pellets. After 72 hr the pellets were removed and 18-24 hr later the above perfusion procedure was repeated. The amount of morphine collected in the perfusate during the washout with naloxone was elevated, compared to the amount collected during the corresponding time of the washout with vehicle for both naive and withdrawn groups. The enhanced morphine release during the washout with naloxone did not differ significantly between the naive and withdrawn rats. However, significantly less morphine was recovered in the perfusate collected during the vehicle washout from the withdrawn rats, compared to that collected from the naive rats. The data suggest that in vivo morphine is specifically bound to receptors and is sensitive to naloxone displacement. It is also concluded that morphine is differentially taken up or otherwise disposed of by brains of rats which are in opiate withdrawal.