Elevated startle during withdrawal from acute morphine: a model of opiate withdrawal and anxiety

Abstract

These data demonstrate that both spontaneous and precipitated withdrawal from an acutely administered opiate produce anxiety-like effects on acoustic startle. This paradigm may be useful in the study of anxiety and the early mechanisms of drug dependence.

Increased Dopamine Receptor Activity in the Nucleus Accumbens Shell Ameliorates Anxiety during Drug Withdrawal

“…Startle data were collapsed across both intensities (95/105 dB) before further statistical analysis, as the magnitude of withdrawal-potentiated startle does not depend on startle stimulus intensity (Harris and Gewirtz, 2004). As there were no effects of order of treatment in any experiment, data were also collapsed across test days.…”

“…In each experiment, one-way analysis of variance (ANOVA) was conducted to verify that animal weights and baseline startle amplitudes did not differ between experimental groups. Changes in startle or activity after experimental treatment were calculated as the percent change from baseline on the same day, that is, percent change ¼ ((testÀbaseline)/ baseline) Â 100 (Harris and Gewirtz, 2004). Data were evaluated for outliers with the Grubb's extreme studentized deviate test with a significance level of a ¼ 0.01.…”

“…To better understand how drug-induced changes in dopaminergic signaling contribute to withdrawal behaviors, we evaluated the effects of intracerebrally infused dopamine receptor agonists on potentiation of the acoustic startle reflex ('withdrawal-potentiated startle') during opiate withdrawal (Harris and Gewirtz, 2004;Rothwell et al, 2009;Cabral et al, 2009). Increases in startle following drug exposure likely represent the anxiety-like component of the withdrawal state.…”

“…Increases in startle following drug exposure likely represent the anxiety-like component of the withdrawal state. For example, potentiated startle during withdrawal is relieved by a second drug exposure or administration of anxiolytic compounds (Harris and Gewirtz, 2004;Rothwell et al, 2009;Engelmann et al, 2009, Radke et al, 2011. The timing of the withdrawal-potentiated startle effect following morphine also coincides with the decrease in drug levels in the brain (Barjavel et al, 1995;Hipps et al, 1976).…”

Episodic Withdrawal Promotes Psychomotor Sensitization to Morphine

“…While monitoring the development of psychomotor sensitization during daily morphine exposure in rats, we concurrently measured the severity of individual withdrawal episodes using the acoustic startle reflex, a validated index of anxiety in humans and animals (Davis et al, 2010) that is reliably elevated during withdrawal from acute opiate exposure (Cabral et al, 2009;Harris and Gewirtz, 2004;Kalinichev and Holtzman, 2003;Rothwell et al, 2009). Not only did the initial severity of withdrawal predict the eventual degree of psychomotor sensitization, but pharmacological manipulations that reduce or exacerbate withdrawal also caused parallel changes in the degree of sensitization.…”