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.
Abstract— In rats, the release of centrally formed 5‐hydroxyindoleacetic acid (5‐HIAA) into brain and spinal cord perfusates and urine was measured. Data from spinal cord perfusion of anaesthetized rats indicate that more than about 36% of the spinal production (122ng/h) of 5‐HIAA is eliminated via the cerebrospinal fluid (CSF). More than 30% of cerebrally formed 5‐HIAA (265.0 ng/h) was calculated to be released into ventricular‐cisternal perfusates. Of the total amount of 5‐HIAA found in the urine we estimated that about 8% originates in the central nervous system (CNS).
In probenecid treated animals there was a substantial increase in the outflow of 5‐HIAA in both perfusion systems. In the combined perfusion experiments no proportional increase of the cerebral contribution to the cisternal outflow was found after probenecid. Our data indicate that a significant proportion of centrally formed 5‐HIAA is eliminated by the CSF. No evidence was found for an increased contribution of cerebral 5‐HIAA to lumbar CSF after application of the probenecid test. Urinary levels of 5‐HIAA do not reflect quantitatively central 5‐hydroxytryptamine metabolism.
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