Lack of sensitization to the effects of d-amphetamine and apomorphine on sensorimotor gating in rats |
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Authors: | J P Druhan M A Geyer R J Valentino |
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Institution: | (1) Department of Psychiatry, University of Pennsylvania, Medical Research Service, Philadelphia Veterans Administration Medical Center, Philadelphia, PA 19104, USA, US;(2) Department of Psychiatry, Allegheny University of the Health Sciences, MS 403, Broad & Vine Streets, Philadelphia, PA 19102, USA, US;(3) Department of Psychiatry, 0804, University of California at San Diego, La Jolla, CA 92093-0804, USA, US |
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Abstract: | This study assessed whether repeated injections of d-amphetamine or apomorphine could induce sensitization to the disruptive effects of these psychomotor stimulants on sensorimotor
gating in rats. In the first experiment, rats were given six pre-exposures to either 2.0 mg/kg d-amphetamine or saline before being tested for the effects of d-amphetamine (0.0, 0.5, 1.0, 2.0 or 4.0 mg/kg, IP) on prepulse inhibition of acoustic startle (PPI) and locomotor activity.
The tests for PPI confirmed that sensorimotor gating could be disrupted by a high dose of d-amphetamine (4.0 mg/kg). However, comparison of the dose-response curves for the drug and saline pre-exposed groups did not
reveal evidence for sensitization to this d-amphetamine effect in drug-pre-exposed rats, despite indications that sensitization had developed to the locomotor stimulant
effects of d-amphetamine. A similar pattern of results was obtained in a second experiment that examined the effects of apomorphine (0.0,
0.1, 0.2, 0.4 and 0.8 mg/kg, SC) on PPI and locomotion in rats pre-exposed to 2.0 mg/kg of this drug or its vehicle. These
findings demonstrate that treatments which induce sensitization to the behavioral activating effects of psychomotor stimulants
do not necessarily produce sensitization to the disruptive effects of stimulants on sensorimotor gating. The implications
of these results for hypotheses linking sensitization-like processes to the etiology of schizophrenia are discussed.
Received: 15 May 1997/Final version: 7 July 1997 |
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Keywords: | Prepulse inhibition Sensorimotor gating Sensitization Locomotor activity Amphetamine Apomorphine Schizophrenia Startle Dopamine Rat |
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