Neurobiology of opioid addiction

Sammanfattning: Since the use of opioids started to emerge for analgesic reasons in the 19th century with the synthetization of morphine, opioids have been studied rigorously to better understand its effects on the brain. This thesis shows that both the analgesic effects and the reinforcing effects of opioids are mediated by the same receptor, the mu opioid receptor (MOR). MOR activity has been correlated to both primary and secondary reinforcers and should be considered to cause positive reinforcement together with increases in dopamine transmission for all drugs of abuse, and not only in relation to opioids. Opioid tolerance, dependence and even addiction are to some extent thought to relate to opioids’ acute effect of cyclic adenosine monophosphate (cAMP) superactivation. Based upon these findings, the allostasis theory of addiction is considered to be the most suitable in defining opioid addiction. The theory claims that the mesolimbic dopamine system becomes sensitized, increasing the attractiveness of opioids. This while counteradaptation increases the pleasurable tolerance of opioids, encouraging the user to increase its intake for the same initial reward. Furthermore the theory claims that cAMP superactivation is causing an unfolding effect of neurobiological and neurochemical expressions which leads to the disorder of addiction. cAMP superactivation is mediating the negatively reinforcing aspects of opioid addiction together with changes to corticotropin-releasing factor (CRF) in the brain stress system, such as the hypothalamic-pituitary-adrenal (HPA) axis and the extended amygdala.