Ž . European Journal of Pharmacology 405 2000 89–101 www.elsevier.nlrlocaterejphar Endogenous opioids and reward Jan M. Van Ree ) , Raymond J.M. Niesink, Leo Van Wolfswinkel, Nick F. Ramsey, Ž . Marleen L. M.W. Kornet, Wouter R. Van Furth, Louk J.M.J. Vanderschuren, Mirjam A.F.M. Gerrits, Caroline L. Van den Berg Department of Pharmacology, Rudolf Magnus Institute for Neurosciences, Utrecht UniÕersity, UniÕersiteitsweg 100, 3584 CG Utrecht, Netherlands Accepted 28 June 2000 Abstract The discovery of endogenous opioids has markedly influenced the research on the biology of addiction and reward brain processes. Evidence has been presented that these brain substances modulate brain stimulation reward, self-administration of different drugs of abuse, sexual behaviour and social behaviour. There appears to be two different domains in which endogenous opioids, present in separate and distinct brain regions, are involved. One is related to the modulation of incentive motivational processes and the other to the performance of certain behaviours. It is concluded that endogenous opioids may play a role in the vulnerability to certain diseases, such as addiction and autism, but also when the disease is present, such as alcoholism. q 2000 Elsevier Science B.V. All rights reserved. Keywords: Endogenous opoid; Addiction; Reward; Brain stimulation reward; Self-administration; Sexual behaviour; Social behaviour 1. Introduction Opium, morphine, and related drugs were fascinating substances for the ancient Greeks but also for people of the 21st century. These substances can control pain quite well in many patients, but can also evoke addiction. The con- cepts of addiction have changed following the discovery of neuropeptides in the brain that mimic the action of mor- Ž . phine endogenous opioids and of the presence in the brain of the machinery for the process of dependence. Endogenous opioids have been implicated in pain relief and addiction, but also in brain reward processes. Be- haviours in which reward plays an important role may be controlled or at least be modulated by endogenous opioid systems. In this article, some of the findings on this topic of the last decades are summarised and discussed, with special emphasis on the procedures used in our laboratory, i.e. drug self-administration, intracranial electrical self- Ž . stimulation ICSS , sexual behaviour and social behaviour Ž . Van Ree and De Wied, 1988 . ) Corresponding author. Tel.: q 31-30-2538807; fax: q 31-30-2539032. Ž . E-mail address: j.m.vanree@med.uu.nl J.M. Van Ree . 2. Reinforcement Alterations in the organism’s environment trigger sen- sory mechanisms and, thus, generate information, which is Ž . then conveyed to the central nervous system CNS . This information and other inputs into the brain are integrated at several levels and can activate or inhibit the brain output systems, including motor systems, thus eliciting be- havioural changes. The purpose of these behavioural changes is the adaptation of an organism to changes in environmental conditions, with the ultimate result that the survival of the organism or its species is ensured. The extreme of an environmental continuum is that the organ- Ž . ism approaches a desirable pleasant and avoids a noxious Ž . aversive environment. The setpoint of behavioural reactions is determined by genetic factors, but its value is continuously modulated by new experiences and, as a consequence, by acquired be- havioural patterns. Behavioural reactions can be acquired through the association of stimuli that are originally neu- tral to innate reactions. The processes involved are types of associative learning. Two major classes of associative learning are distinguished: classical and instrumental con- ditioning. During classical conditioning, a concept which 0014-2999r00r$ - see front matter q 2000 Elsevier Science B.V. All rights reserved. Ž . PII: S0014-2999 00 00544-6