Dependence and cross-dependence in the guinea-pig myenteric plexus

Abstract

Chronic activation of opioid receptors results in the development of tolerance and dependence. Tolerance may be confined to a single receptor type and thus has been termed "selective tolerance". The present investigation reveals that prolonged activation of an inhibitory acting receptor type not only results in dependence associated with this receptor but also brings about cross-dependence. Cross-dependence involves both opioid receptors as well as nonopioid receptors, e.g. adrenoceptors. The experimental design employed did not permit conclusions to be drawn about whether those receptors exhibiting cross-dependence also developed tolerance. Regardless of the receptors and their specific subsequent transduction systems, all the receptors which showed dependence and cross-dependence proved sensitive to pertussis toxin, suggesting a critical function of GTP-binding proteins for the development of not only opioid dependence but also for drug dependence in general. Since multiple transmitter receptors may converge on the same ion channel, the concept of "convergent dependences" may be linked to GTP-binding proteins. However, no conclusions can be drawn with regard to the precise biochemical mechanisms underlying dependence.