Studies of the behavioral pharmacology of buprenorphine and other opioid mixed agonist-antagonist drugs are proposed. The opioid mixed agonist-antagonists are powerful analgesics with minimal capacity for induction of physical dependence. Buprenorphine is also potentially effective for the treatment of opiate addiction. Buprenorphine, butorphanol, nalbuphine and pentazocine have been shown to be reinforcers in the primate drug self-administration model but little is known about the relative reinforcing characteristics of these compounds. We proposed to compare the relative reinforcing efficacy of a series of opioid mixed-agonist-antagonists with heroin, a prototype opiate agonist, in a primate drug self-administration model using established operant procedures. Progressive ratio procedures are a powerful technique to compare the relative reinforcing efficacy of drugs. Since buprenorphine has a relatively long duration of action the effects of varying the frequency of buprenorphine access on its reinforcing profile will also be examined. A second goal is to examine the effects of two new pharmacotherapies for the treatment of opiate abuse (buprenorphine and naltrexone) on the reinforcing properties of non-opioid drugs which are commonly abused by methadone-maintained patients. A prototype stimulant (cocaine), barbiturate (methohexital), benzodiazepine (triazolam) and opiate agonist (heroin) will be studied. The effects of maintenance treatment with buprenorphine and naltrexone on the reinforcing properties of these drugs will be compared in a primate drug self-administration model. If buprenorphine or naltrexone treatment modifies the reinforcing efficacy of non-opioid drugs, this would enhance the therapeutic usefulness of these compounds and contribute to prevention of secondary drug abuse problems in opiate addicts. The effects of buprenorphine maintenance treatment on the self-administration of other opioid mixed agonist-antagonist drugs will also be examined. Buprenorphine has both kappa and mu antagonist activity, and nalbuphine, butorphanol and pentazocine each have kappa agonist activity. Data obtained should clarify the behavioral effects of interactions between mixed agonist-antagonist analgesics with different putative opioid receptor binding affinities.
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