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Journal of Neuroscience, Vol 11, 2703-2712, Copyright © 1991 by Society for Neuroscience
Amphetamine, cocaine, and fencamfamine: relationship between locomotor and stereotypy response profiles and caudate and accumbens dopamine dynamics
R Kuczenski, DS Segal and ML Aizenstein
Department of Psychiatry, University of California, San Diego, La Jolla 92093.
Using in vivo microdialysis, the caudate and nucleus accumbens dopamine
(DA) responses to the psychomotor stimulants amphetamine (AMPH), cocaine
(COC), and fencamfamine (FCF) were evaluated in rats concurrent with
characterization of their behavioral response profiles. Doses of each
stimulant that produced either enhanced locomotion or a prolonged period of
intense focused stereotypies were examined to evaluate the quantitative
relationships between stimulant-induced behaviors and changes in DA
dynamics and to test the hypothesis that a balance between mesostriatal and
mesolimbic DA activity contributes to the appearance of specific
stimulant-induced behaviors. Although 10 mg/kg COC and 1.7 mg/kg FCF
promoted levels of locomotor activity substantially greater than 0.5 mg/kg
AMPH, the magnitude of the DA increases in both caudate and accumbens were
markedly less than was obtained following AMPH. Thus, stimulant-induced
locomotion appears to be dissociated from the quantitative DA response in
both brain regions. This behavioral/DA dissociation was also apparent at
higher doses of AMPH (2.5 mg/kg), COC (40 mg/kg), and FCF (6 mg/kg), doses
that promoted a behavioral pattern that included a prolonged period of
intense stereotypy. Indeed, the regional DA responses to these high doses
of COC and FCF were substantially less than the response to 0.5 mg/kg AMPH.
Furthermore, there were no differences in the ratio of the caudate and
accumbens DA responses as a function of dose for any of the three drugs.
Thus, the balance between the regional DA activation does not appear to
regulate the expression of the behavioral response. Additionally, the
effects of these stimulants on regional DA metabolite concentrations were
compared. The results indicate that AMPH promoted an identical pattern of
effects on caudate and accumbens DA metabolites, suggesting that similar
mechanisms govern the dynamics of DA in response to AMPH in both brain
regions. In contrast, the DA uptake blockers promoted some region-specific
effects on DA metabolites that may be due to regional differences in the DA
metabolism and rates of impulse flow.
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