CHANGES IN PLASMA-CORTICOSTERONE LEVELS AS A MEASURE OF ACUTE DEPENDENCE UPON LEVORPHANOL IN RATS

Abstract

Changes in plasma corticosterone levels were utilized as a sensitive and reliable indicator of opiate withdrawal. By using rats prepared with chronic indwelling i.v. catheters, drug injections and sequential blood sampling were accomplished in conscious undisturbed animals. Acute administration of levorphanol tartrate (LT) at 0.5, 1.0 or 2.0 mg/kg body wt. caused an elevation in circulating corticosterone. With the lowest dose of LT, hormone levels returned to pretreatment values by 180 min. Naloxone hydrochloride (NX), 0.4 mg/kg, administered 3 h after pretreatment with LT, 0.5 mg/kg, produced a significant elevation in plasma corticosterone. Animals pretreated with saline did not show the same increase in hormone levels after NX. NX, administered at several doses, along with LT, suppressed the plasma corticosterone increase which is normally observed when LT is given acutely. When NX is administered at sufficient dosage, along with LT pretreatment, the subsequent administration of the antagonist did not elicit the withdrawal response. Data indicate that a similar increase in plasma corticosterone, upon challenge with NX after a single dose of morphine, generalizes to other opiates. Blockade of the initial rise in plasma corticosterone and subsequent increase upon injection of the antagonist raise the probability of the responses being related and opiate specific.