Prepulse inhibition during withdrawal from an escalating dosage schedule of amphetamine.
BACKGROUND
Psychomotor stimulants can induce psychotic states in humans that closely resemble those observed in patients with idiopathic schizophrenia. Attentional and sensorimotor gating impairments are observed in schizophrenic patients using the latent inhibition (LI) and prepulse inhibition (PPI) behavioral assays, respectively. Our previous studies demonstrated that after 4 days of withdrawal from a period of amphetamine (AMPH) administration, animals exhibited disrupted LI but normal PPI.


OBJECTIVE
The aim of the present study was to test PPI in AMPH-withdrawn rats under experimental conditions similar to those used to best demonstrate locomotor sensitization following AMPH withdrawal.


METHODS
We examined the effects on PPI of (1) pairing drug injections with PPI test-associated cues, (2) administration of a low-dose dopamine agonist challenge and (3) testing following longer withdrawal periods (23, 30, 60 days).


RESULTS
Although none of these conditions revealed a disruption of PPI in AMPH-withdrawn rats, we did observe that the acoustic startle response was reduced during a restricted time period following AMPH withdrawal. Similar to our previous findings, AMPH-withdrawn animals showed disrupted LI on day 16 of withdrawal and locomotor sensitization to a challenge injection of AMPH after 62 days of withdrawal.


CONCLUSIONS
We conclude that the effects of repeated AMPH on PPI are not modulated by the same experimental parameters known to be important for eliciting locomotor sensitization and that withdrawal from the schedule of AMPH administration used in this study models only specific cognitive dysfunctions linked to schizophrenic symptoms, since LI was disrupted but PPI was not affected.
Russig
Holger
H
Laboratory of Behavioural Neurobiology, Swiss Federal Institute of Technology (ETH Zurich), Postfach Schorenstrasse 16, 8603 Schwerzenbach, Switzerland.
Murphy
Carol A
CA
Feldon
Joram
J
D000161:Acoustic Stimulation; D000704:Analysis of Variance; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D003214:Conditioning, Classical / Q000187:drug effects*; D003463:Cues; D003913:Dextroamphetamine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D007266:Inhibition, Psychological; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013216:Reflex, Startle / Q000187:drug effects; D013239:Stereotyped Behavior / Q000187:drug effects*; D013375:Substance Withdrawal Syndrome / Q000523:psychology*; D013997:Time Factors
D000697:Central Nervous System Stimulants; D003913:Dextroamphetamine