Can biophysical models of dendritic spines be used to explore synaptic changes associated with addiction?

Abstract Effective treatments that prevent or reduce drug relapse vulnerability should be developed to relieve the high burden of drug addiction on society. This will only be possible by enhancing the understanding of the molecular mechanisms underlying the neurobiology of addiction. Recent experimental data have shown that dendritic spines, small protrusions from the dendrites that receive excitatory input, of spiny neurons in the nucleus accumbens exhibit morphological changes during drug exposure and withdrawal. Moreover, these changes relate to the characteristic drug-seeking behavior of addiction. However, due to the complexity of dendritic spines, we do not yet fully understand the processes underlying their structural changes in response to different inputs. We propose that biophysical models can enhance the current understanding of these processes by incorporating different, and sometimes, discrepant experimental data to identify the shared underlying mechanisms and generate experimentally testable hypotheses. This review aims to give an up-to-date report on biophysical models of dendritic spines, focusing on those models that describe their shape changes, which are well-known to relate to learning and memory. Moreover, it examines how these models can enhance our understanding of the effect of the drugs and the synaptic changes during withdrawal, as well as during neurodegenerative disease progression such as Alzheimer’s disease.