Progressive ratio performance maintained by buprenorphine, heroin and methadone in Macaque monkeys.
The relative reinforcing efficacy of buprenorphine (0.01-0.10 mg/kg/inj.), heroin (0.01-0.10 mg/kg/inj.), methadone (0.03-0.25 mg/kg/inj.) and saline were compared in Macaque male monkeys using progressive ratio procedures. Responding for drugs and food (1 g banana pellet) was maintained on a second order FR 4 (VR 16:S) schedule of reinforcement that required an average of 64 responses for each injection or food pellet. After 40 sessions (10 days) of stable performance, the number of responses for each drug injection was systematically increased until monkeys reached a breakpoint defined by 2 consecutive days of no drug injections. Progressive ratio breakpoints for heroin at intermediate and high doses (0.05 and 0.10 mg/kg/inj.) were two to three times higher than for any other drug (P less than 0.05). Breakpoints for buprenophine (0.01-0.10 mg/kg/inj.) were higher than for a low dose of methadone (0.03 mg/kg/inj.) but were equivalent to an intermediate methadone dose (0.10 mg/kg/inj.). Breakpoints for both low (0.01 mg/kg/inj.) and high (0.10 mg/kg/inj.) buprenorphine doses were greater than for intermediate doses (0.03 and 0.05 mg/kg/inj.) but these differences were not statistically significant. Linear regression and area under the curve analyses were used to quantify the rate at which drug maintained responding decreased by 30% of control levels as response requirements were increased. Extrapolated breakpoints derived from linear regression analyses were significantly correlated (P less than 0.05-0.01) with actual breakpoints for buprenorphine, heroin and methadone. The concordance between 'extrapolated' and traditional breakpoint ranking of these drugs suggests that regression analysis techniques can be used to predict traditional breakpoints.
Alcohol and Drug Abuse Research Center, McLean Hospital, Harvard Medical School, Belmont, MA 02178.
N K
NK
Mello
S E
SE
Lukas
M P
MP
Bree
J H
JH
Mendelson
D000818:Animals; D002047:Buprenorphine / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D003932:Heroin / Q000494:pharmacology*; D008253:Macaca mulatta; D008254:Macaca nemestrina; D008297:Male; D008691:Methadone / Q000494:pharmacology*; D009042:Motivation / Q000187:drug effects*; D012055:Reinforcement Schedule; D012646:Self Administration
D002047:Buprenorphine; D003932:Heroin; D008691:Methadone