Anxiogenic-like effects of opiate withdrawal seen in the fear-potentiated startle test, an interdisciplinary probe far drug-related motivational states

Rationale: Anxiety-like effects may be universal to withdrawal from drugs o f abuse. The study of withdrawal would benefit from the acoustic startle re sponse (ASR), a discrete, cross-species reflex which is increased by fear-r elated states. However, existing reports of opiate-related effects on basel ine ASR have not validated ASR as a measure of drug-related motivation. Obj ective: The effects of opiate treatment and withdrawal were examined using fear-potentiated startle, a startle test more sensitive to fear than baseli ne changes. Methods: Fear-conditioned rats were treated with Alzet osmotic pumps delivering 0.25 mg/kg per day fentanyl or placebo pumps. Experiment 1 examined changes before and during opiate treatment on locomotor activity and baseline, prepulse inhibition, and fear-potentiated startle. Experiment 2 examined the same responses during withdrawal precipitated after 4-7 day s of treatment using IV naloxone. Results: Experiment 1 revealed an attenua ted fear-potentiated startle on the first test after the start of fentanyl treatment (4 h); this was not seen on subsequent tests and suggested tolera nce to this acute effect, Experiment 2 found an enhancement of fear-potenti ated startle precipitated in fentanyl-treated rats after injection of 0.025 and 0.16 mg/kg naloxone; this was not seen at 1 mg/kg naloxone, even thoug h more physical withdrawal signs were most prevalent at this dose. In neith er experiment did locomotor activity, baseline ASR, or prepulse inhibition of the ASR show any treatment effect. Conclusions: Fear-potentiated startle may provide a specific and valid measure of anxiety-like effects of drug w ithdrawal. Discussed were conditions needed to see this effect and the rele vance of the findings for different mechanisms of withdrawal discomfort.