%0 Journal Article %A T. Bushell %A T. Endoh %A A. A. Simen %A D. Ren %A V. P. Bindokas %A R. J. Miller %T Molecular Components of Tolerance to Opiates in Single Hippocampal Neurons %D 2002 %R 10.1124/mol.61.1.55 %J Molecular Pharmacology %P 55-64 %V 61 %N 1 %X We examined the effect of acute and chronic opioid treatment on synaptic transmission and μ-opioid receptor (MOR) endocytosis in cultures of naı̈ve 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. %U https://molpharm.aspetjournals.org/content/molpharm/61/1/55.full.pdf