Can biophysical models give insight into the 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 to 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 input from excitatory neurons, from 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 the 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 wellknown 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 disease progression.