The aim of these studies was to examine whether
amphetamine-induced sensitization in rats could be used as an animal model to study the basis of certain abnormalities seen in
schizophrenia. Specifically, these experiments examined whether rats subjected to a sensitizing regimen of
amphetamine would show the sensorimotor gating and greater
amphetamine-induced displacement of radio-
raclopride binding deficit that is observed in
schizophrenia. In the first experiment, animals were divided into two groups with each rat receiving an
intraperitoneal injection of
amphetamine (AMPH) or saline (SAL) (1 ml/kg) three times per week for 3 weeks for a total of nine
injections. AMPH dose was increased weekly from 1 mg/kg in the first week to 3 mg/kg in the third. Twenty-two days after the last injection, prepulse inhibition (PPI) of the acoustic startle response was tested. In addition, rats were tested for the effects of a challenge dose of 0.5 mg/kg AMPH on locomotor activity and [3H]
raclopride (RAC) binding potential (BP) in the striatum. The tests for PPI confirmed that sensorimotor gating was disrupted in the AMPH-induced sensitized-state rats at baseline. The AMPH-sensitized rats also exhibited higher locomotor response to AMPH and a lower binding of striatal [3H]
raclopride when challenged with the
drug. The results were replicated and even more pronounced in rats that were treated with AMPH for 5 weeks, with doses ranging from 1mg/kg in the first week to 5 mg/kg in the fifth. These sensorimotor gating deficits and neurochemical (greater AMPH-induced displacement of radio-
raclopride binding) abnormalities show similarities with the pathophysiology of
schizophrenia and suggest that the AMPH-sensitized-state rats could be used to model certain aspects of
schizophrenia.