PRECLINICAL STUDY: Morphine withdrawal decreases responding reinforced by sucrose self-administration in progressive ratio

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Previous studies have shown that withdrawal from psychostimulant drugs such as d-amphetamine or methamphetamine decreases motivation to work for a natural reinforcement, which is thought to be associated with the withdrawal-induced depressive state and hypofunction of the mesolimbic dopamine system. However, to our knowledge, studies exploring the effect of morphine withdrawal on motivation for a natural reinforcement are lacking. The purpose of the present study was to examine whether motivation to work for a natural reinforcement changes during morphine withdrawal. Three groups of male Sprague–Dawley rats were trained to respond on a nose poke for a 4% sucrose solution under a progressive ratio schedule and were subsequently administered a 10-day regimen of injection of high or low dose of morphine or saline. Their duration of break point and withdrawal symptoms were assessed. The finding showed that break points were significantly reduced on day 1 and persisted to at least day 10 of withdrawal without change in locomotor activity. There were hardly any differences bear mentioning when comparing the magnitude of the decrease between the high- and the low-dose group, whereas the withdrawal scales were significant greater in the high-dose group than in the low-dose group. The results suggest that the morphine withdrawal resulted in decreased motivation to obtain the natural reinforcement. The progressive ratio procedure may be a useful technique for evaluation of changes in motivation for natural reinforcing stimuli following withdrawal from opiates.

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