Novel form of drug-dependence--on adenosine in guinea pig ileum

There is evidence that dependence on opiates occurs in neurones bearing their specific receptors, whose activation inhibits the neurone. Thus, incubation of guinea pig ileum with an opiate induces in the final cholinergic motoneurone of the myenteric plexus a dependence that closely resembles in basic characteristics opiate dependence in whole animals. A comparable, but distinct dependence can be induced by incubating the ileum with clonidine. Since adenosine also inhibits the final cholinergic motoneurone, by activating a specific purine receptor, we have tested whether it, too, can induce a distinct dependence in this neurone. To demonstrate dependence, we challenged the ileum by removing drug or by adding the selective purine receptor antagonist, 8-phenyltheophylline, which does not substantially inhibit phosphodiesterase, or caffeine. We found that incubation of the ileum with adenosine, or with the more potent derivative, 2-chloroadenosine, induced a novel form of drug dependence, made manifest by withdrawal of inducing drug, but not by antagonists of opiates or clonidine.