DIAZEPAM INDUCES TOLERANCE IN THE ISOLATED SKIN OF PLEURODEMA THAUL

The effects of the long-term administration of diazepam on the potenti al difference and short-circuit current of the isolated skin of the to ad Pleurodema thaul (P. thaul) were investigated. Diazepam applied in a concentration range of 4.6 x 10(-6) to 5.2 x 10(-5) M decreased both electrical parameters. This response was unaffected by flumazenil ind icating that the action of diazepam is not induced through benzodiazep ine receptors. Induction of tolerance to diazepam on its observed effe cts on potential difference and short-circuit current was obtained by the administration of a single dose of the drug in a slow release prep aration. Skins tolerant to diazepam were also tolerant to the acute ef fects of verapamil on both electric parameters. Tolerance to diazepam effects was partly reversed by increasing Ca2+ concentration in the in ner bathing solution. The results are consistent with a Ca2+ channel b locking effect of diazepam in the P. thaul skin.