Individual variation in response to µ opiate receptor challenge-past, present, and future: a “personal” history of investigation

Individual differences in response to addictive substances may provide important clues to the mechanisms underlying drug action, addiction, reward, and reward-related disease states. Early psychoneuroendocrinological studies have led to the distinction of responders and nonresponders upon µ opiate receptor agonist administration. The systematic analysis of the gene encoding the µ opiate receptor reveals abundant DNA sequence diversity, suggesting numerous individually different forms of the gene. The present work illustrates the challenges of establishing complex genotype-phenotype relationships in the presence of high natural sequence variation, and provides some preliminary solutions. Progress in the future is expected to come from whole systems analysis-based approaches, integrating variation in all genes in all pathways.