Effects of buprenorphine, methadone, and cariprazine on economic choice between remifentanil and food in squirrel monkeys

Abstract

We recently reported an economic choice task in which squirrel monkeys chose between differing amounts of remifentanil, a fast-acting opioid, or a food reward to develop a preclinical screen for evaluating potential pharmacotherapies for opioid dependence. Herein, two known opioid addiction treatments are evaluated using this task, as well as a potential new agent, cariprazine, a dopamine D2/D3 receptor partial agonist currently used to treat bipolar disorder and schizophrenia. Preclinical rodent studies suggest this class of compounds may reduce opiate self-administration. Squirrel monkeys were pretreated daily with clinically relevant doses of each compound during the five days of treatment evaluation using the economic choice task. Shifts in drug preference were measured as changes in subjects' indifference values, where the probability of drug and milk choice are equivalent. Buprenorphine produced a significant shift in indifference value between baseline and treatment weeks, indicating a decrease in drug preference. Subjects treated with methadone and cariprazine did not show any significant shift in drug preference. Differences between the buprenorphine and methadone results likely reflect a lack of opioid dependence in the subjects. The cariprazine results suggest that it does not alter opioid reward in non-dependent primates over a five day period.

Keywords: buprenorphine; cariprazine; economic choice task; methadone; opioid; opioid maintenance therapy; remifentanil.

Figure 1:

Choice allocation curves of buprenorphine and methadone pretreatments compared to contemporaneous baseline. Curves represent the group average choice over the last 3 days of each respective week. A) Buprenorphine 0.1 mg/kg produced a significant shift in IndV, p = 0.01. B) Buprenorphine 0.32 mg/kg also produced a significant shift in IndV, p = 0.002. C) Methadone at 1.0 mg/kg did not change choice allocation between remifentanil and milk.

Figure 2:

Choice allocation curves of cariprazine pretreatments for baseline and treatment weeks, as presented in Fig. 1 A) Cariprazine at 10 μg/kg, B) 30 μg/kg, and C) 100 μg/kg did not change choice allocation between remifentanil and milk.