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Vol. 282, Issue 2, 561-573, 1997
Department of Psychiatry, School of Medicine, University of
California of San Diego at La Jolla, California
Stimulant psychosis and addiction are most commonly associated with
repeated, high-dose binges or runs, typically preceded by a more
intermittent pattern of stimulant abuse. We previously reported that
rats exposed to an escalating dose-run pattern of amphetamine
administration exhibited changes in their behavioral response profile
that differed both qualitatively and quantitatively from the response
to either acute or intermittent daily treatment. To determine the
generality of these effects and characterize further the nature of the
behavioral and neurochemical changes of this treatment, rats received
single daily injections of amphetamine (2.5 or 4.0 mg/kg s.c.) or
equimolar doses of methamphetamine, followed by multiple runs (four
daily injections at 2-hr intervals) with the pretreatment dose. This
treatment resulted in a unique behavioral profile, including a profound
increase in the relative expression of locomotion vs.
stereotypy. The markedly enhanced poststereotypy locomotor activation
was characterized by repeated "burst"-like episodes of ambulation.
The number of runs required for the emergence of this behavior was dose
dependent and was similar for the two drugs except that with
methamphetamine, there also was a marked prolongation of the
poststereotypy locomotor response during run exposures. During runs,
both drugs produced a decline in the caudate but not the nucleus
accumbens microdialysate dopamine response, whereas only
methamphetamine produced a decline in the serotonin response that was
apparent in both regions. The possible relationship between these
behavioral and neurochemical changes and their implications for high
dose patterns of stimulant abuse are discussed.
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