? One fundamental question facing drug abuse researchers is why some people become addicted to drugs while others do not. Previous research has shown that rats reared in an enriched environment, with cohorts and novel objects, do not self-administer stimulants to the same degree as isolated rats. Thus far, however, the underlying mechanism is unknown. It is well known, however, that environmental factors (e.g. stress, drugs, learning) alter gene transcription. It is also known that manipulating gene transcription can alter behavioral responses to a given environment. The present proposal investigates gene transcription as one underlying mechanism for the addiction-protected behavioral phenotype resulting from environmental enrichment. First, transgenic reporter mouse lines will be used to understand how acute novelty affects gene transcription and, more importantly, how repeated novelty (environmental enrichment) alters transcriptional responses to amphetamine. Second, levels and changes in transcription factors and addiction-related proteins will be studied under similar conditions. Third, transcription factors will be over-expressed in enriched and isolated animals to see if enrichment alters transcription-mediated effects on amphetamine-stimulated behavior. It is hoped that these studies will provide greater insight into individual differences in susceptibility to drug addiction. ? ? ? ?
