ITF mapping after drugs of abuse: pharmacological versus perceptional effects

Analysis of inducible transcription factors (ITFs) expression is often applied to map drug-induced changes of neuronal activity in brain. Administration of cocaine and alcohol induces ITFs in a large number of brain structures. However, induction of ITFs in a brain region does not necessarily indicate a pharmacological effect of the drug in this brain region. Many of the brain regions could be activated by secondary effects. Perception of stimulus properties of the drug or locomotor effects of the drug are possible secondary effects. Anesthesia can block induction of ITFs by cocaine and alcohol suggesting that ITF expression in a majority of brain regions is more sensitive to secondary effects than to pharmacological effects of these drugs. In agreement with this hypothesis is our finding that the majority of brain regions responding with ITF expression to alcohol administration do not respond to voluntary alcohol self-administration in animals. Only a few brain regions show similar ITF induction after both administration and self-administration of this drug. Presumably these brain regions could be responding to pharmacological effects of alcohol. Given the low resolution of invasive techniques, ITF mapping experiments will continually contribute to our understanding of mechanisms of drug addiction and alcoholism.