No abstract

No abstract

We examined the effect of acute and chronic opioid treatment on synaptic transmission and -opioid receptor (MOR) endocytosis in cultures of naïve rat hippocampal neurons. Opioid agonists that activate MOR inhibited synaptic transmission at inhibitory but not excitatory autapses. [D-Ala 2 ,N-Me-Phe 4 ,Gly 5 -ol]-enkephalin (DAMGO), morphine, and methadone were all effective at blocking inhibitory transmission. These same drugs also reduced the amplitude of voltage-dependent Ca 2ϩ 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 ␤-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.

1 The profile of opioid and cannabinoid receptors in neurons of the nucleus tractus solitarius (NTS) has been studied using the whole-cell configuration of the patch clamp technique. 6 Mainly N-and P/Q-type VDCCs were inhibited by both DAMGO and Orphanin FQ, while L-type VDCCs were inhibited by WIN55,122. 7 These results suggest that m-and k-opioid receptors and ORL-1 receptor inhibit N-and P/Q-type VDCCs via Ga i -protein bg subunits, whereas CB1 receptors inhibit L-type VDCCs via Ga i -proteins involving PKA in NTS.

It is recognized that brain contains all the components of the renin-angiotensin systems (RAS). The nucleus of the tractus solitarius (NTS) is