Dopamine depletion abolishes apomorphine- and amphetamine-induced increases in extracellular serotonin levels in the striatum of conscious rats: a microdialysis study
Section snippets
Animals
Animal studies were performed in compliance with National Institutes of Health (NIH) guidelines, following review and approval by the institutional animal care and use committee (IACUC) at McLean Hospital. All efforts were made to minimize the number of animals used and their suffering. Sprague–Dawley rats initially weighing 200–225 g were purchased from Taconic Farms (Germantown, NY, USA), housed two per cage, kept on a 12-h light/dark cycle (on 07:00–19:00 h) with standard rat chow and water
Results
Baseline levels of DA and 5-HT in striatal dialysate from intact animals averaged 1.65±0.5 (N=16) and 0.15±0.04 (N=19) nM, respectively (Table 1). In 6-OHDA-lesioned animals baseline levels of DA in striatal dialysates were below detection levels and 5-HT averaged 0.59±0.2 (N=15) nM (Table 1). This was a significant increase (0.59 versus 0.20 nM, 31 df, t=−2.03, P=0.05) in baseline 5-HT levels in lesioned animals (Table 1).
Two-way ANOVA for 5-HT levels revealed a significant effect of lesion
Discussion
Apomorphine-induced striatal efflux of 5-HT was abolished in 6-OHDA-lesioned animals. d-Amphetamine also failed to increase 5-HT levels in 6-OHDA-lesioned animals. Our results are consistent with the hypothesis that DA has a stimulatory action on 5-HT neurotransmission in intact brain. Systemic apomorphine (0.5 mg/kg, s.c) was previously reported to increase 5-HT concentrations in dialysates from corpus striatum and hippocampus (Mendlin et al., 1998). Local administration of apomorphine (1–100
Acknowledgements
This work is supported by Udall Parkinson's Disease Research Center of Excellence grants P50 NS39793, NARSAD Young Investigator Award and Theodore and Vada Stanley Foundation. We also thank Dr. Lanya Hayden for her help in preparation of this manuscript and Dr. Ross Baldessarini for helpful comments.
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