U.S. Department of Defense


Date of this Version



Published in Neuropharmacology 61 (2011) 1088-1096; doi:10.1016/j.neuropharm.2011.01.028


Opiates are among the most powerful analgesics and pain-relieving agents. However, they are potentially extremely addictive thereby limiting their medical use, making them exceedingly susceptible to abuse and adding to the global drug problem. It is believed that positive memories associated with the pleasurable effects of opiates and negative memories associated with dysphoria during opiate withdrawal contribute to compulsive opiate-seeking behavior characterizing addiction. There is a vast amount of available data regarding the neuroadaptations in response to opiates during opiate tolerance, dependence and withdrawal that contribute to opiate addiction, yet it is still a major challenge to identify the neurobiological adaptations that underlie the hallmarks of opiate addiction such as compulsive drug use, and relapse to drug seeking. Since the discovery of synaptic plasticity as the cellular correlate of learning and memory, strong overlaps between neural and cellular substrates of learning and addiction have been recognized. Consequently, the current notion of addiction supports the idea that aberrant forms of drug induced synaptic plasticity and learning in the brain drive addictive behaviors. Here we discuss current progress on some of the recently identified forms of synaptic plasticity at excitatory and inhibitory synapses in opioid-sensitive areas of the brain that are targeted by opiates and other addictive drugs. The neuroadaptations involved in opiate tolerance, dependence and withdrawal will be re-visited since they share many features with synaptic learning mechanisms.