Project: Research project

Project Details


These studies are designed to increase our understanding of the
neurochemical mechanisms relevant to cocaine and opioid abuse, which is
critical for the development of effective treatment strategies. Cocaine,
morphine, and heroin are widely abused substances that activate dopamine-
rich regions of the brain, and many studies suggest that there are
interactions between the actions of psychomotor stimulants and opioids.
The objective of this project is to examine what role opioid receptors
play in the development of tolerance and sensitization to cocaine and the
manner by which cocaine interacts with opioid receptors. Chronic
continuous cocaine administration produces large increases in locomotor
activity, to which rats become partially tolerant over several days.
Continuous morphine administration produces moderate increases in
locomotor activity which remain constant. When co-administered, they
produce levels of activity greater than either drug alone, and the
tolerance that is observed to cocaine is less pronounced. Studies
examining the mechanism by which this effect occurs are currently
underway. Chronic treatment with an opioid receptor antagonist produces
an increase in the number of mu-opioid receptors in the brain. There are
also increases in opioid receptor function following chronic antagonist
administration, i.e. an increase in receptor regulation of second
messenger function in vitro, and of opioid analgesia in vivo. These
receptors are also increased in specific brain regions following chronic,
continuous cocaine treatment. An opioid agonist such as morphine
produces a down-regulation (decrease) of_mu-opioid receptors, and
tolerance to opioid analgesia. When cocaine and morphine are chronically
co-administered, there is a loss of tolerance normally associated with
chronic morphine treatment. These findings, together with the in vitro
receptor and functional assays, suggest that the effects of chronic
cocaine on mu-opioid receptors are similar to those seen following opioid
antagonist treatment. Since cocaine does not bind to opioid receptors,
this effect is likely via an indirect action (eg. release of an agent
that binds to opioid receptors or a heterologous regulation of receptors
regulating common transduction systems). Treatment with a selective
inhibitor of either dopamine, norepinephrine, or serotonin had no effect
on opioid receptors, suggesting that cocaine may not exert its opioid
altering effects through any individual system, but may require the
combination of two, or all three systems. Further examination of the
effects of these compounds on opioid receptor function are underway.
These findings suggest that cocaine has a unique interaction with the
opioid system. Thus, this system may serve as a target for the
development of medical therapies for cocaine abuse which would result in
a substantial betterment of the public health through a limitation on the
spread of cocaine abuse and HIV infection.
StatusNot started


  • National Institute on Drug Abuse
  • National Institute on Drug Abuse
  • National Institute on Drug Abuse


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