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

Abstract

There is evidence that dependence on opiates occurs in neurones bearing their specific receptors, whose activation inhibits the neurone¹. 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^2–6. A comparable, but distinct dependence can be induced by incubating the ileum with clonidine⁷. Since adenosine also inhibits the final cholinergic motoneurone, by activating a specific purine receptor^8,9, 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^10–13. We found that incubation of the ileum with adenosine, or with the more potent derivative, 2-chloroadenosine^14–16, induced a novel form of drug dependence, made manifest by withdrawal of inducing drug, but not by antagonists of opiates or clonidine.