PT  - JOURNAL ARTICLE
AU  - Bushell, T.
AU  - Endoh, T.
AU  - Simen, A. A.
AU  - Ren, D.
AU  - Bindokas, V. P.
AU  - Miller, R. J.
TI  - Molecular Components of Tolerance to Opiates in Single Hippocampal Neurons
AID  - 10.1124/mol.61.1.55
DP  - 2002 Jan 01
TA  - Molecular Pharmacology
PG  - 55--64
VI  - 61
IP  - 1
4099  - http://molpharm.aspetjournals.org/content/61/1/55.short
4100  - http://molpharm.aspetjournals.org/content/61/1/55.full
SO  - Mol Pharmacol2002 Jan 01; 61
AB  - 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.