LONG-TERM SENSITIZATION TO THE BEHAVIORAL-EFFECTS OF NALTREXONE IS ASSOCIATED WITH REGIONALLY SPECIFIC CHANGES IN THE NUMBER OF MU-OPIOID AND DELTA-OPIOID RECEPTORS IN RAT-BRAIN

Enhanced sensitivity to some of the behavioral effects of the opioid a ntagonist naltrexone (NTX) develops following once-weekly injections o f cumulative doses of the drug. Rats treated with this regimen of NTX injections show enhanced sensitivity to the operant response rate decr easing effects of NTX and NTX-induced salivation. The enhanced sensiti vity is long-lasting and appears to be produced through conditioning p rocesses. We have conducted saturation binding assays to assess possib le changes in the number and affinity of mu and delta opioid receptors in cortical, midbrain and hindbrain membrane preparations from Long-E vans rats treated once weekly for 8 weeks with cumulative doses of the drug (1, 3, 10, 30 and 100 mg/kg). H-3-DAMGO (0.5-21 nM) and H-3-pCl- DPDPE (0.04-4 nM) were used to characterize mu and delta receptors, re spectively. NTX treatment had no effect on H-3-DAMGO binding in cortex , but decreased binding in midbrain and increased binding in hindbrain relative to saline-treated controls. Saturation analyses revealed tha t these differences reflected changes in the number, but not the affin ity of mu receptors. NTX treatment also increased the amount of H-3-pC l-DPDPE bound to delta receptors in midbrain and hindbrain, but not in cortex. Again, these changes were due to changes in the number of rec eptors. Thus, chronic NTX differentially affects the number of mu and delta opioid receptors in various brain regions.