Abstract
Background and Aim:
There is evidence that a buprenorphine/naltrexone combination may be effective as a relapse prevention not only for opioid abuse, but for polydrug abuse, yet little work has been carried out to determine the optimum ratio of the two drugs. A significant problem with this treatment strategy arises from the fact that buprenorphine and naltrexone need to be administered by different routes. However, both buprenorphine and naltrexone can be delivered transdermally using iontophoresis, and we are cur-rently using this technique to develop a buprenor-phine/naltrexone combination therapy that is effective in reducing relapse to polydrug abuse.
Method:
Using conditioned place preference (CPP) in male Sprague-Dawley rats, the rewarding properties of buprenorphine and naltrexone combinations were assessed. The ability of buprenorphine/naltrexone to inhibit drug-primed reinstatement of morphine-induced CPP was then tested.
Results:
Buprenorphine alone (0.3 mg/kg) was rewarding, whereas a buprenorphine to naltrexone ratio of 1:10 (0.3 and 3 mg/kg) was aversive. However, a ratio of 1:3 (0.3 and 1 mg/kg) was neither rewarding nor aversive. A morphine priming dose of 2.5 mg/kg reinstated morphine CPP (animals were trained to demonstrate CPP with 10 mg/kg morphine followed by extinction training), an effect that was inhibited by prior administration of buprenorphine/naltrexone (0.3 and 1 mg/kg respectively). All drugs were administered ip
Conclusions:
We have demonstrated a combination of buprenorphine/naltrexone with no rewarding or aversive effects that appears to inhibit reinstatement in an animal model of drug-seeking behavior. Ongoing work is designed to further test the ability of buprenorphine/naltrexone to prevent CPP reinstatement, and to optimise conditions for their transdermal delivery.
There is evidence that a buprenorphine/naltrexone combination may be effective as a relapse prevention not only for opioid abuse, but for polydrug abuse, yet little work has been carried out to determine the optimum ratio of the two drugs. A significant problem with this treatment strategy arises from the fact that buprenorphine and naltrexone need to be administered by different routes. However, both buprenorphine and naltrexone can be delivered transdermally using iontophoresis, and we are cur-rently using this technique to develop a buprenor-phine/naltrexone combination therapy that is effective in reducing relapse to polydrug abuse.
Method:
Using conditioned place preference (CPP) in male Sprague-Dawley rats, the rewarding properties of buprenorphine and naltrexone combinations were assessed. The ability of buprenorphine/naltrexone to inhibit drug-primed reinstatement of morphine-induced CPP was then tested.
Results:
Buprenorphine alone (0.3 mg/kg) was rewarding, whereas a buprenorphine to naltrexone ratio of 1:10 (0.3 and 3 mg/kg) was aversive. However, a ratio of 1:3 (0.3 and 1 mg/kg) was neither rewarding nor aversive. A morphine priming dose of 2.5 mg/kg reinstated morphine CPP (animals were trained to demonstrate CPP with 10 mg/kg morphine followed by extinction training), an effect that was inhibited by prior administration of buprenorphine/naltrexone (0.3 and 1 mg/kg respectively). All drugs were administered ip
Conclusions:
We have demonstrated a combination of buprenorphine/naltrexone with no rewarding or aversive effects that appears to inhibit reinstatement in an animal model of drug-seeking behavior. Ongoing work is designed to further test the ability of buprenorphine/naltrexone to prevent CPP reinstatement, and to optimise conditions for their transdermal delivery.
| Original language | English |
|---|---|
| Pages (from-to) | 257 |
| Number of pages | 1 |
| Journal | Pharmacological Reports |
| Volume | 63 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Jan 2011 |
| Event | European Opioid Conference 2011 - Krakow, Poland Duration: 1 Jan 2011 → … |