Augmented levels of tolerance and physical dependence in rats self-administering morphine compared to those passively receiving the drug

Abstract

<p>Two physiological changes (namely tolerance and physical dependence) reliably emerge following repeated exposure to the opiate drugs and are considered to be important contributors to the behavioural state of addiction. As such, they are often induced in experimental subjects prior to examining addictive behaviour. An assumption implicit in such work is that the physiological effects of passively-administered drugs are equivalent to those of actively self-administered drugs. Two experiments are presented which demonstrate that the development of both tolerance and physical dependence is attenuated in rats passively receiving morphine compared to those self-administering identical doses of the drug. An additional experiment found evidence for the ability of a schedule of passive drug delivery to attenuate physical dependence and tolerance established through drug self-administration. Furthermore, in all three experiments, tolerance and physical dependence were found to develop rapidly and reliably following the self-administration of surprisingly small doses of morphine. One means by which self-administration might facilitate the acquisition of tolerance and physical dependence is through the inherently greater predictability of self-administered drug doses. An experiment designed to assess whether increased signalling of impending drug doses would likewise facilitate the acquisition of tolerance and physical dependence failed to demonstrate any such effect.</p>