Pharmacological regulation of gene expression was one of the top professional interests of Dr. Costa. He promoted the idea that drugs can improve the endogenous mechanisms of synaptic plasticity by modulating gene expression. In this article I reflect upon Dr. Costa's leadership in projects undertaken at FGIN that were aimed at elucidating how neurotransmitter receptor activation could affect brain function by modulating genes and their products. I will be presenting examples of how pharmacological tools can change gene expression. These include the ability of drugs of abuse to alter the synthesis of opioid peptides or an endogenous ligand for GABAA receptor. I will conclude with a brief summary of intriguing discoveries about the regulation of nerve growth factor (NGF) and its receptors by beta-receptor agonists, adrenal steroids and cytokines.