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Repeated administration of amphetamine induces sensitisation to its disruptive effect on prepulse inhibition in the rat.

Journal article
Authors Jianhua Zhang
Jörgen Engel
Bo Söderpalm
Lennart Svensson
Published in Psychopharmacology
Volume 135
Issue 4
Pages 401-6
ISSN 0033-3158
Publication year 1998
Published at Institute of Physiology and Pharmacology
Institute of Physiology and Pharmacology, Dept of Pharmacology
Pages 401-6
Language en
Keywords Acoustic Stimulation, Adrenal Cortex Hormones, metabolism, Adrenalectomy, Amphetamine, administration & dosage, pharmacology, Animals, Central Nervous System Depressants, pharmacology, Central Nervous System Stimulants, administration & dosage, pharmacology, Haloperidol, pharmacology, Male, Rats, Rats, Sprague-Dawley, Reflex, Startle, drug effects
Subject categories Basic Medicine, Pharmacology, Neuroscience


Male Sprague-Dawley rats were repeatedly treated with amphetamine (AMP, 1 mg/kg, SC) at 3- day intervals for 15 days and tested for prepulse inhibition of acoustic startle after each treatment. This treatment regimen induced sensitisation in the animals as evidenced by a progressive increase in the disruptive effect of AMP on prepulse inhibition. Persistent changes in brain function was indicated, since an increase in disruptive effect was observed in sensitised animals also after a 22-day-long drug- and test-free period. The development of sensitisation was blocked by pretreatment with haloperidol (HPD, 0.1 mg/kg, SC), which suggests that sensitisation to the disruptive effect of AMP was dependent on dopamine (DA) D2 receptor activation. Furthermore, the development of sensitisation was blocked by adrenalectomy, which suggests that sensitisation was dependent also on circulating adrenal hormones. Increased DA-ergic activity has been implicated in the pathophysiology of schizophrenia and AMP-induced sensitisation to the neuronal functions that modulate prepulse inhibition may be an experimental model to investigate this hypothesis.

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