Sally L Huskinson1, Kevin B Freeman, William L Woolverton. 1. Division of Neurobiology and Behavior Research, Department of Psychiatry and Human Behavior, The University of Mississippi Medical Center, 2500 N. State Street, Jackson, MS, 39216, USA, shuskinson@umc.edu.
Abstract
RATIONALE: Cocaine and opioids are often co-abused. Laboratory research has focused largely on the reinforcing effects of mixtures of drugs relative to the drugs alone. Less research has examined drug mixing by the subject under concurrent-access conditions. OBJECTIVE: Self-administration of various doses of cocaine and remifentanil was examined under concurrent-access conditions. It was hypothesized that if cocaine and opioid combinations were more effective reinforcers than the single drugs, subjects would mix the two drugs by adjusting their responding to cocaine and an opioid alternative to maintain an optimal ratio of cocaine/remifentanil intake. METHOD: Three male rhesus monkeys were allowed to self-administer cocaine (0.05-0.2 mg/kg/inj) or saline on one lever and remifentanil (0.05-0.4 μg/kg/inj) or saline on the other lever under concurrent fixed-ratio (FR) 10 schedules. Daily sessions lasted 2 h, and there was a 1-s timeout after every 10-s injection. RESULTS: When saline and drug were concurrently available, responding on the saline-associated lever was low relative to the drug alternative. When cocaine and remifentanil were concurrently available, both drugs were self-administered above saline levels. Cocaine intake decreased, and remifentanil intake increased as a function of the remifentanil dose that was available. Conversely, cocaine intake and remifentanil intake did not change systematically as a function of the cocaine dose that was available. CONCLUSION: Monkeys will mix cocaine and an opioid when the two drugs are available concurrently. However, there was no indication that monkeys titrated drug intake to maintain an optimal ratio of intake of the two compounds.
RATIONALE: Cocaine and opioids are often co-abused. Laboratory research has focused largely on the reinforcing effects of mixtures of drugs relative to the drugs alone. Less research has examined drug mixing by the subject under concurrent-access conditions. OBJECTIVE: Self-administration of various doses of cocaine and remifentanil was examined under concurrent-access conditions. It was hypothesized that if cocaine and opioid combinations were more effective reinforcers than the single drugs, subjects would mix the two drugs by adjusting their responding to cocaine and an opioid alternative to maintain an optimal ratio of cocaine/remifentanil intake. METHOD: Three male rhesus monkeys were allowed to self-administer cocaine (0.05-0.2 mg/kg/inj) or saline on one lever and remifentanil (0.05-0.4 μg/kg/inj) or saline on the other lever under concurrent fixed-ratio (FR) 10 schedules. Daily sessions lasted 2 h, and there was a 1-s timeout after every 10-s injection. RESULTS: When saline and drug were concurrently available, responding on the saline-associated lever was low relative to the drug alternative. When cocaine and remifentanil were concurrently available, both drugs were self-administered above saline levels. Cocaine intake decreased, and remifentanil intake increased as a function of the remifentanil dose that was available. Conversely, cocaine intake and remifentanil intake did not change systematically as a function of the cocaine dose that was available. CONCLUSION: Monkeys will mix cocaine and an opioid when the two drugs are available concurrently. However, there was no indication that monkeys titrated drug intake to maintain an optimal ratio of intake of the two compounds.
Authors: Kevin B Freeman; Jennifer E Naylor; Thomas E Prisinzano; William L Woolverton Journal: Psychopharmacology (Berl) Date: 2014-01-31 Impact factor: 4.530
Authors: Eduardo R Butelman; Carina Y Chen; Kimberly J Lake; Kate G Brown; Mary Jeanne Kreek Journal: Exp Clin Psychopharmacol Date: 2020-10-29 Impact factor: 3.157
Authors: C Austin Zamarripa; William S Doyle; Kevin B Freeman; James K Rowlett; Sally L Huskinson Journal: Exp Clin Psychopharmacol Date: 2022-01-31 Impact factor: 3.492