Withdrawal from repeated amphetamine administration leads to disruption of prepulse inhibition but not to disruption of latent inhibition.
The present study represents a continuous effort to develop an animal model of schizophrenia based on the "endogenous dopamine sensitization" hypothesis. To achieve this goal, withdrawal from an escalating amphetamine (AMPH) regime administration [three injections per day over a period of 4 days and increasing doses from 1 to 10 mg/kg of AMPH or an equivalent volume of saline (SAL)] was employed. Animals exposed to this treatment were evaluated on their performance in attentional (Latent inhibition, LI) and sensorimotor gating (Prepulse inhibition, PPI) tasks in a drug free state and tested for locomotor sensitization following a low dose of AMPH challenge administration.LI using active avoidance, tested on withdrawal day 4, was unaffected. PPI of the acoustic startle response, measured on withdrawal days 6 and 70, was disrupted. On the 76th day of withdrawal, a low challenge dose of AMPH (1 mg/kg) led to a clear locomotor sensitization effect.
Peleg-Raibstein
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D
Laboratory of Behavioural Neurobiology, Swiss Federal Institute of Technology (ETH Zurich), Schwerzenbach, Switzerland.
Sydekum
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E
Russig
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H
Feldon
J
J
D000161:Acoustic Stimulation; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000009:adverse effects*; D003627:Data Interpretation, Statistical; D003913:Dextroamphetamine / Q000009:adverse effects*; D006185:Habituation, Psychophysiologic / Q000187:drug effects*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013216:Reflex, Startle / Q000187:drug effects*; D013375:Substance Withdrawal Syndrome / Q000523:psychology*
D000697:Central Nervous System Stimulants; D003913:Dextroamphetamine