CHANGES IN SENSITIVITY TO THE RATE-DECREASING EFFECTS OF OPIOIDS IN PIGEONS TREATED ACUTELY OR CHRONICALLY WITH L-ALPHA-ACETYLMETHADOL

The purpose of this study was to examine the effects of acute and chro nic treatment with I-alpha-acetylmethadol (LAAM), a long-acting mu opi oid agonist that is used to treat opioid dependence. In pigeons respon ding under an FR20 schedule of food presentation, LAAM decreased respo nding in a dose- and time-dependent manner, with the largest decrease occurring 4 hr after the administration of 5.6 mg/kg. Acute (1.0-5.6 m g/kg) or chronic (1.0-5.6 mg/kg/day) treatment with LAAM decreased sen sitivity to morphine and increased sensitivity to naltrexone, although for both drugs changes in sensitivity were 3- to 10-fold greater duri ng chronic treatment. Chronic LAAM treatment (5.6 mg/kg/day) also decr eased sensitivity to fentanyl and etonitazene by 3-fold and increased sensitivity to nalorphine and nalbuphine by 30- and 6-fold, respective ly; sensitivity to enadoline and ketamine increased only 2- to 3-fold. When LAAM treatment was temporarily suspended for 1 day, response rat es decreased to 33% of control; this disruption was reversed by acute administration of morphine or etonitazene. Increased sensitivity to na ltrexone and disruptions in responding when LAAM treatment was tempora rily suspended indicate that dependence developed to LAAM. Tolerance a nd cross-tolerance to agonists as well as increased sensitivity to ant agonists can be similar during chronic treatment with morphine or LAAM ; however, increased sensitivity to nalbuphine during LAAM treatment i s not typically observed during morphine treatment, suggesting that de pendence on LAAM might not be identical to dependence on morphine, Fin ally, changes in sensitivity to other drugs might predict altered sens itivities to opioids and nonopioids in humans receiving LAAM.