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.