The pleasant effects of opium were already known 6000 years ago and opium has been used for medical purposes for at least 3500 years. Opium, and its r.1ain constituent morphine, evoke a feeling of well-being and always relieve pain of any origin, in other words, a perfect analgesic and euphoric drug. However, there are unpleasant repercussions. Thus, the pleasant effects are followed by a period of dysphoria. With the first, moderate dose of opiate this rebound is not important. But euphoric and analgesic effects disappear with repeated administration unless the dose is steadily increased. When the opiate is withcirawn after repeated administration of high doses, the dysphoric rebound wi 11 gain dangerous proportions and this is one of the reasons for continued (addicted) use of the opiate. Thus, the perfect analgesic and euphoric drug produces a perfect dependence. One of the most important stimuli to the promotion of research into the mechanism of action of opiates is the desire to control opiate-dependence. Such control would help two groups of users: those who need a strong analgesic would not necessarily become dependent and those who become dependent would not necessarily always need opiates. The acute effects of morphine are highly interrelated phenomena such as analgesia and euphoria, while dependence is ascribed to an adaptation of the cells of the body. In order to relate or dissociate these effects of opiates it is necessary to analyse the eel lular and molecular events related to the acute effects of the opiate. If these cellular and molecular events are the same as those underlying opiate-dependence, it will not be possible to dissociate the analgesic and euphoric effects of opiates from their ability to produce dependence. However, if it appears that differences do exist between the mechanism of these two opiateinduced phenomena then control of opiate-dependence may be possible. In the experiments described here, the effects of acute morphine administration on dopaminergic neurons in the rat were investigated. Dopamine is an important neurotransmitter in 1 imbic and extrapyramidal brain areas and plays an important role in the integration of emotional responses. Furthermore, the analgesic and rewarding (euphoric?) properties of morphine have been related inter alea to interactions with dopaminergic systems. An attempt has been made to analyse molecular mechanisms involved in the action of morphine on dopaminergic neurons in different brain areas and to analyse the relation of both these actions and behavioural responses to acute morphine administration.

J. Bruinvels
Erasmus University Rotterdam
Erasmus MC: University Medical Center Rotterdam