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.
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http://dx.doi.org/10.1007/s00213-014-3661-8 | DOI Listing |
Am J Otolaryngol
December 2024
Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN, United States of America. Electronic address:
Purpose: Our institution uses two approaches for nasal mucosal preparation during endoscopic sinus surgery (ESS) to improve surgical field visualization: topical epinephrine (TE) versus topical cocaine with injection of lidocaine containing epinephrine (TCLE). We aimed to compare anesthetic outcomes after ESS using these techniques.
Methods And Materials: We retrospectively identified adult patients at our institution who underwent ESS from May 2018 through January 2023 under general anesthesia with propofol and remifentanil infusions.
Behav Neurosci
June 2023
Department of Psychology, University of Cambridge.
Most people sample addictive drugs, but use becomes disordered in only a small minority. Two important factors that influence susceptibility to addiction are individual differences in personality traits and biological sex. The influence of traits on addiction-like behavior is well-characterized in preclinical models of cocaine self-administration, but less is understood in regards to opioids.
View Article and Find Full Text PDFNeuropharmacology
April 2023
Warren Center for Neuroscience Drug Discovery, Vanderbilt University School of Medicine, Nashville, TN, 37232, USA; Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN, 37232, USA; Vanderbilt Institute of Chemical Biology, Vanderbilt University, Nashville, TN, 37232, USA. Electronic address:
Recent evidence suggests that inhibition of the M muscarinic acetylcholine receptor (mAChR) may provide a novel non-opioid mechanism for the treatment of opioid use disorder (OUD). Previous studies from our group and others have demonstrated that acute administration of the long-acting M negative allosteric modulator (NAM) ML375 attenuates established self-administration of cocaine, ethanol, oxycodone, and remifentanil in rats. In the present study, we characterized the effects of acute and repeated administration of the novel, short-acting M NAM VU6008667 on the reinforcing effects of oxycodone and reinstatement of oxycodone-seeking behaviors in male Sprague-Dawley rats, as well as on physiological withdrawal from oxycodone.
View Article and Find Full Text PDFSci Rep
December 2022
Department of Cell Biology, Duke University, Durham, NC, USA.
Genetically tractable animal models provide needed strategies to resolve the biological basis of drug addiction. Intravenous self-administration (IVSA) is the gold standard for modeling psychostimulant and opioid addiction in animals, but technical limitations have precluded the widespread use of IVSA in mice. Here, we describe IVSA paradigms for mice that capture the multi-stage nature of the disorder and permit predictive modeling.
View Article and Find Full Text PDFJ Pharmacol Exp Ther
December 2022
Department of Psychiatry & Human Behavior, Center for Innovation & Discovery in Addictions, University of Mississippi Medical Center, 2500 N State Street, Jackson, Mississippi.
This study evaluated the reinforcing effects of fentanyl, alone or in combination with the benzodiazepine alprazolam, in rhesus monkeys (3 females, 3 males). Subjects were trained to self-administer the opioid remifentanil (0.3 g/kg/injection) under a progressive-ratio schedule of reinforcement.
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