Anxiogenic-like effects of opiate withdrawal seen in the fear-potentiated startle test, an interdisciplinary probe far drug-related motivational states
M. Fendt et Rf. Mucha, Anxiogenic-like effects of opiate withdrawal seen in the fear-potentiated startle test, an interdisciplinary probe far drug-related motivational states, PSYCHOPHAR, 155(3), 2001, pp. 242-250
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.