Addiction is a complex brain disease, whose molecular and cellular underpinnings remain largely
unknown. Repeated drug use induces long-term plasticity in various brain areas that is considered to
potentially trigger further compulsive use. Converging evidence has revealed that memory and
addiction share both neural circuitry and molecular mechanisms. While many studies investigated
the mesocorticolimbic system, the hippocampus has become a region of interest. Matrix assisted
laser desorption and ionization mass spectrometry imaging (MALDI-MSI) presents a unique ability to
map the toxicodynamic changes associated to drugs of abuse. In this study, the acute effect of
cocaine in rat brain was investigated with or without co-administration of alcohol. Brain tissue
sections for each condition were analyzed using a MALDI-MSI in negative polarity after 9-
aminoacridine (9-AA) deposition on the tissue surface. Multivariate analysis including principal
component analysis (PCA) and spatial shrunken centroids have been performed to differentiate the
metabolic profiles in hippocampus according to the type of administration. This study offers
promising results showing the potential of MSI for investigating the metabolomic changes in the
brain associated with drug consumption. It may bring new insights into the study of toxicodynamic
responses of cocaine consumption in reward-learning related regions.