Effects of etonitazene consumption and abstinence on the signal transmission of mu-opioid receptors in brain membranes of rats.

Rats, for 8 weeks consuming the mu-opioid agonist etonitazene (forced and free choice conditions yielding high and low drug-consumers), were sacrificed after 2 days or 6 weeks lasting drug deprivation. Binding characteristics of membranes from the parieto-occipital cortex of these four groups were compared with those of drug-naive controls. In all five groups, 1 microM of the mu-opioid receptor agonist [D-Ala2,N-MePhe4,Gly5-ol]enkephalin (DAMGO) increased the guanosine-5'-O([35S]3'thio)triphosphate ([35S]GTPgammaS) binding activity on guanine nucleotide-binding (G) proteins, and 500 nM of GTPgammaS decreased the [3H]DAMGO binding affinity. During acute withdrawal, both opioid consuming groups displayed a higher maximum efficacy (Emax) in basal [35S]GTPgammaS binding (34 and 31%, each P < 0.01), but only the forced group showed a 58% higher net DAMGO-stimulated binding density Bmax (P < 0.01) and 53% more activated G proteins per mu-opioid receptor (P < 0.05). In the presence of GTPgammaS both groups revealed a higher affinity in [3H]DAMGO binding (each 25%, P < 0.01). The long-term drug-deprived groups displayed no differences in their binding characteristics.