ANXIOGENIC-LIKE EFFECTS OF SPONTANEOUS AND NALOXONE-PRECIPITATED OPIATE WITHDRAWAL IN THE ELEVATED PLUS-MAZE

Withdrawal from opiates and other drugs of abuse in human addicts is a ssociated with a state of anxiety that may be of motivational relevanc e for the maintenance of drug addiction. Previous attempts with rats t o model the anxiogenic-like effects of opiate withdrawal using the ele vated plus-maze have met with mixed success. The current study sought to determine whether spontaneous and naloxone-precipitated opiate with drawal could be observed reliably in rats made dependent on morphine t hrough implantation of two morphine pellets (75 mg morphine base each) . Seventy-two hours after implantation of either morphine or placebo p ellets, rats were tested in the elevated plus-maze. In Experiment 1, p ellets were removed 8 or 12 h prior to test; results indicated an anxi ogenic-like effect (reduction in time spent in the open arms) of opiat e withdrawal at 8 but not 12 h postpellet removal. In Experiment 2, pe llets were not removed, but withdrawal was precipitated with naloxone (0.003-0.03 mg/kg SC). Naloxone dose dependently precipitated a reduct ion in exploration of the open arms of the plus-maze. The results sugg est that both spontaneous and precipitated withdrawal from continuous morphine administration via pellet implantation result in demonstrable anxiogenic-like effects in the plus-maze. (C) 1998 Elsevier Science I nc.