Amphetamine-sensitized animals show a sensorimotor gating and neurochemical abnormality similar to that of schizophrenia.
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.
Tenn
Catherine C
CC
Schizophrenia/PET Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
Fletcher
Paul J
PJ
Kapur
Shitij
S
D000161:Acoustic Stimulation; D000661:Amphetamine / Q000633:toxicity*; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000503:physiopathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D008297:Male; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D009433:Neural Inhibition / Q000187:drug effects* / Q000502:physiology; D020891:Raclopride / Q000493:pharmacokinetics; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000502:physiology; D013216:Reflex, Startle / Q000187:drug effects* / Q000502:physiology; D012559:Schizophrenia / Q000139:chemically induced* / Q000503:physiopathology; D012684:Sensory Thresholds / Q000187:drug effects* / Q000502:physiology
D017448:Receptors, Dopamine D2; D020891:Raclopride; D000661:Amphetamine