In vivo measures of monoamines during amphetamine-induced behaviors in rats.
1. Using a removable in vivo microdialysis probe, and remote sample collection, the temporal and dose-related behavioral and monoamine response to amphetamine (AMPH) were examined in freely-moving rats. Extracellular dopamine, serotonin and their metabolites were monitored concomitant with detailed characterization of the locomotor and stereotypy profiles. Consistent with previous results, AMPH (0.5-5.0 mg/kg) induced a rapid dose-dependent increase in dopamine concentration and decrease in the concentrations of the dopamine metabolites. Dopamine and metabolites exhibited contrasting temporal and dose-related patterns, suggesting that the decline in dopamine metabolites is functionally dissociated from the AMPH-enhanced dopamine release, and that metabolite levels do not provide an accurate index of functional dopaminergic activity. 2. Dose response comparisons revealed a significant relationship between AMPH-induced increases in behavioral perseveration and the magnitude and duration of the dopamine release. However, the temporal patterns of the neurotransmitter response and individual components of stereotypy were not parallel, suggesting that the presence of stereotypies is not associated simply with quantitative differences in striatal dopamine release. 3. Consistent with this interpretation, we found that a variety of manipulations including reserpine, apomorphine, and chronic amphetamine pretreatment, produced a dissociation between the alterations in the behavioral and dopaminergic responses to amphetamine. The behavioral response to amphetamine may be influenced by the interaction between levels of dopamine and serotonin, by the state of their respective receptors, and by the relative contributions of additional dopaminergic systems.
Kuczenski
R
R
Department of Psychiatry, University of California, San Diego, La Jolla.
Segal
D S
DS
D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D001679:Biogenic Amines / Q000032:analysis / Q000502:physiology*; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D003956:Dialysis / Q000379:methods; D004298:Dopamine / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D007700:Kinetics; D008832:Microchemistry; D009043:Motor Activity / Q000187:drug effects*; D051381:Rats; D012110:Reserpine / Q000494:pharmacology*; D012701:Serotonin / Q000502:physiology*; D013239:Stereotyped Behavior / Q000187:drug effects*; D013997:Time Factors
D001679:Biogenic Amines; D012701:Serotonin; D012110:Reserpine; D000661:Amphetamine; D004298:Dopamine