Volume 17, Number 7,
Issue of April 1, 1997
pp. 2551-2566
Copyright ©1997 Society for Neuroscience
An Escalating Dose "Binge" Model of Amphetamine Psychosis:
Behavioral and Neurochemical Characteristics
Received Aug. 6, 1996; revised Dec. 4, 1996; accepted Dec. 6, 1996.
David S. Segal and
Ronald Kuczenski
Psychiatry Department, University of California, San Diego,
School of Medicine, La Jolla, California 92093
Stimulant-induced psychosis is most frequently associated with a
chronic, high-dose, multiple daily ("binge") exposure pattern of
stimulant abuse. To simulate these conditions, rats were exposed to
escalating doses of amphetamine (Escalating Dose phase, 1.0-8.0 mg/kg)
before multiple daily injections of relatively high doses of the drug
(Run phase, 8.0 mg/kg/2 hr × 4 injections). Behavior was
monitored continuously during the course of these treatments as well as
during subsequent amphetamine challenges at various times after
discontinuation of drug treatment. With the Escalating Dose-Run
pattern of administration, a unique behavioral profile emerged in which
tolerance occurred to the amount of time spent engaged in continuous
focused stereotypy simultaneous with a profound increase in ambulatory
activity that appeared agitated and disorganized. Parallel in
vivo microdialysis studies showed progressively declining extracellular dopamine and serotonin responses, both within and between
successive runs, whereas the norepinephrine response remained relatively unaltered. We propose that this model more closely resembles
clinical manifestations of amphetamine psychosis and that the
alterations may reflect a shift in the relative activation of
mesolimbic and nigro-striatal dopamine pathways.
Key words:
amphetamine;
stereotypy;
locomotion;
binge;
psychosis;
microdialysis;
dopamine;
norepinephrine;
serotonin