Dr Jan M. van Ree - 2008

"Love for endorphins and beyond"

Dr. Jan M. van Ree
Chair, Neuroscience Research Programme
UMC Utrecht, The Netherlands

My research career started with setting up drug self- administration in animals in an institute that was pioneering in isolating peptides from pituitary and brain tissue and searching for interesting effect of these peptides on behaviour of rats. Just after the opioid peptides were discovered, isolated beta-endorphin (C- fragment) was shown to induce tolerance and physical dependence, but also self-administration in rats. Subsequently, many studies were directed to unravel the pathophysiological role of endorphins in addictive behaviour with opiates, cocaine and alcohol. Endorphins seem to be involved in various phases of this behaviour: initiation, maintenance and relapse. These peptides are particularly implicated in the individual vulnerability to addiction, the dynamics of daily drug intake, craving and relapse. But different brain opioid systems are concerned in these various processes. Besides addictive behaviour, endorphins have been implicated in social behaviour of young and adult rats, particularly in close and intimate contact in dyadic encounters, and in motivation and performance of sexual behaviour. The pathophysiological role of endorphins was investigated by administering opioid antagonists to animals and humans under various conditions. To mention, stereotypy in tethered sows, the twitch in horses, alcohol intake in monkeys, self-injurious behaviour, premenstrual symptoms in humans, placebo response, schizophrenic patients and autistic children. Of particular interest are studies showing effects of low doses of opioid antagonists e.g. cocaine-induced place preference, play behaviour of young rats and relapse of alcohol intake in monkeys. A characteristic feature of peptide systems is that enzymes convert large peptide molecules to smaller fragments with a distinct biological activity. Enzymes can generate from beta-endorphin alpha- and gamma-type endorphins. Gamma-type endorphins have been shown to induce effects in animals resembling the action of antipsychotic drugs, while alpha-type endorphins exert effects that are comparable with those of amphetamine. Subsequently, gamma-type endorphins were administered with a certain success to schizophrenic patients and shown to control distinct dopaminergic systems. Indeed, research on behavioural effects of endorphins and related peptides has disclosed the (patho)physiological significance of these peptides. This research also shows the complexity and beauty of the functioning of our brain.

Van Ree, Gerrits MAFM, Vanderschuren LJMJ. Pharmacological Reviews 1999; 51 (2): 341-396.