@article {Bushell55, author = {T. Bushell and T. Endoh and A. A. Simen and D. Ren and V. P. Bindokas and R. J. Miller}, title = {Molecular Components of Tolerance to Opiates in Single Hippocampal Neurons}, volume = {61}, number = {1}, pages = {55--64}, year = {2002}, doi = {10.1124/mol.61.1.55}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {We examined the effect of acute and chronic opioid treatment on synaptic transmission and μ-opioid receptor (MOR) endocytosis in cultures of na{\i}̈ve rat hippocampal neurons. Opioid agonists that activate MOR inhibited synaptic transmission at inhibitory but not excitatory autapses. [d-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin (DAMGO), morphine, and methadone were all effective at blocking inhibitory transmission. These same drugs also reduced the amplitude of voltage-dependent Ca2+ currents in inhibitory but not excitatory neurons. Chronic treatment with all three opioids reduced the subsequent effects of a challenge with either the same drug or one of the others in individual autaptic neurons. Chronic treatment with DAMGO or methadone produced internalization of enhanced yellow fluorescent protein-tagged MOR expressed in hippocampal neurons within hours, whereas morphine produced internalization much more slowly, even when accompanied by overexpression of β-arrestin-2. We conclude that DAMGO, methadone, and morphine all produce tolerance in single hippocampal neurons. Morphine-induced tolerance does not necessarily seem to involve receptor endocytosis.}, issn = {0026-895X}, URL = {https://molpharm.aspetjournals.org/content/61/1/55}, eprint = {https://molpharm.aspetjournals.org/content/61/1/55.full.pdf}, journal = {Molecular Pharmacology} }