What are the molecular mechanisms behind tachyphylaxis (downregulation of receptors in response to an agonist?)
There are many mechanisms of receptor down-regulation, including internalisation and degradation e.g for the epidermal growth factor receptor and uncoupling via post-translational modifcation e.g. for G protein-coupled receptors.

In the case of opioid receptors there is emerging evidence that down-regulation is achieved, at least in part, by post-transcriptional regulation by a microRNA. Presumably this could also accompanied by inactivation of existing receptors, but if the adaptation/desenitisation is long-term then normal receptor turnover may be sufficient.