Elsevier

Neuroscience

Volume 119, Issue 1, 18 June 2003, Pages 167-179
Neuroscience

Research paper
The acquisition, retention and reversal of spatial learning in the morris water maze task following withdrawal from an escalating dosage schedule of amphetamine in wistar rats

https://doi.org/10.1016/S0306-4522(03)00045-9Get rights and content

Abstract

Two experiments were carried out to evaluate the effects of amphetamine withdrawal in rats on spatial learning in the water maze. A schedule of repeated d-amphetamine administration lasting for 6 days, with three injections per day (1–5 mg/kg, i.p.), was employed. Experiment 1 demonstrated that amphetamine withdrawal did not impair the acquisition of the water maze task (third to fourth withdrawal days), but amphetamine-withdrawn rats made more target-zone visits and reached the former location of the platform quicker than controls during the probe test (fifth withdrawal day). In experiment 2, retention of the location of the escape platform was assessed in animals having been pre-trained on the water maze task before treatment. On the third withdrawal day, retention of the former platform location was assessed in a probe test. Retention was only clearly seen in the measure of target zone visits, and performance did not differ between groups. Next, the animals were trained to escape to a new location in the water maze on withdrawal days 4–5. A reversal effect could be discerned across the first four trials, as evident by the animals’ tendency to search in the former target quadrant. This interfered with the new learning, but amphetamine-withdrawn animals appeared to overcome it more rapidly than saline-treated controls. This finding is consistent with the view that amphetamine withdrawal can enhance behavioural switching, which could be expressed as a reduction of proactive interference during learning; and, it is in line with our previous finding that latent inhibition is also attenuated during amphetamine withdrawal.

Section snippets

Subjects

Two cohorts of Wistar rats (experiment 1: n=24, experiment 2: n=23; Wistar; 250–350 g) were obtained from our in-house specific-pathogen-free breeding facility. They were caged individually in Macrolon type III cages (48×27×20 cm) and housed in a temperature (21±1 °C) and humidity (55±5%) controlled animal facility under a reversed light/dark cycle (lights on 0600–1800 h). Food (Kliba 3430, Klibamühlen, Kaiseraugst, Switzerland) and water were available ad libitum in the home cages. Behavioural

Visible platform task

This was carried out on the second day of withdrawal, and all animals learned to escape from the water by climbing onto the visible platform. Escape latency and swim distance decreased as training progressed, whilst swim speed increased. Separate 2×4 (treatment×trials) split-plot ANOVAs on these measures all yielded a highly significant effect of trials [latency: F(3,66)=17.58, P<0.0001; swim distance: F(3,66)=8.26, P<0.0001; swim speed: [F(3,66)=9.49, P<0.0001]. There were no significant

Discussion

The present study represents the first attempt to evaluate the effects of withdrawal following an escalating dose schedule of systemic AMPH administration on the classical water maze procedure followed by reversal learning. The schedule of repeated AMPH administration was effective in inducing long-lasting locomotor sensitisation as demonstrated subsequent to the two experiments. We demonstrated that this regimen of AMPH withdrawal impaired neither the acquisition (experiment 1) nor the

Acknowledgments

This study was supported by the Swiss Federal Institute of Technology (ETH-Zurich, Switzerland). We would like to thank the staff of the animal facility for their care and maintenance of the animals used in this study, Mr. Peter Schmid for his valuable technical assistance and Ms. Jane Fotheringham for her editorial help.

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