The treatment of addiction is frustrated by high rates of relapse. These relapses are thought to result from retrieval of drug-related memories and the translation of those memories into goal-directed behavior. Accordingly, addiction can be viewed as a pathological condition of the brain that develops using mechanisms of synaptic plasticity similar to traditional models of learning and memory. The main focus of the CNCR Addiction team is to identify the molecular and cellular underpinnings of an enhanced vulnerability and relapse to drug seeking using rodent models of addiction.

Behavioral models play a central role in this research. They include instrumental learning paradigms in which animals are trained to self-administer drugs of abuse in the presence of environmental cues. This allows accurate analysis of motivational states and conditioned drug seeking processes during distinct stages of the addiction cycle.

In one research line we have a particular focus on acute synaptic changes that take place immediately following re-exposure to drug-conditioned stimuli, and that may lead to resumption of drug seeking. These combined efforts have recently led to the discovery of the first molecular mechanism that may explain why addicts will relapse upon exposure to drug-associated cues. For further reading please see Scientific highlight of the year.
Recently, we became interested in the role of extinction processes and in the manipulation of extinction memories in order to reduce relapse vulnerability. Currently, the molecular components mediating consolidation of extinction memory are being identified.
By focusing on the synaptic proteins in relevant brain areas our research is likely to identify novel drug-targetable synaptic components that may form an entry point for well defined therapeutic targets for the clinical management of relapse behavior in human addicts.

A second research line is devoted to the identification of risk factors that predispose individuals to drug addiction. Our recent work has shown that drug exposure during adolescence results in long-lasting behavioural changes both in the motivational and cognitive domain. In addition, there is evidence for unique drug-induced neuroplasticity underlying these behavioral disturbances.
In other studies, we obtained convincing evidence for a critical role of trait impulsivity in the initiation and persistence of nicotine and alcohol seeking in rodents.
Future studies will take advantage of genetic resources in mice in combination with quantitative synaptic proteomics technology to search for novel genes/proteins determining vulnerability to alcohol and nicotine addiction.

These research lines are supported by two ZON-MW Top grants awarded in 2006 and 2009 and have a strong multidisciplinary character. The PI’s involved include Guus Smit, Sabine Spijker, Huib Mansvelder, Tonny Mulder (ANW) and Tommy Pattij (ANW).