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Altered presynaptic function in monoaminergic neurons of monoamine oxidase-A knockout mice
Article first published online: 22 MAY 2002
DOI: 10.1046/j.1460-9568.2002.01986.x
1460-9568/asset/cover.gif?v=1&s=f24cc0b5582a6f8af7d83eee00b2056f825c5624 "European Journal of Neuroscience")
Additional Information
How to Cite
Owesson, C. Å., Hopwood, S. E., Callado, L. F., Seif, I., McLaughlin, D. P. and Stamford, J. A. (2002), Altered presynaptic function in monoaminergic neurons of monoamine oxidase-A knockout mice. European Journal of Neuroscience, 15: 1516–1522. doi: 10.1046/j.1460-9568.2002.01986.x
Publication History
- Issue published online: 22 MAY 2002
- Article first published online: 22 MAY 2002
- Received 23 October 2001, revised 4 March 2002, accepted 15 March 2002
- Abstract
- Article
- References
- Cited By
Keywords:
- autoreceptors;
- dopamine;
- noradrenaline;
- serotonin;
- transporters
Abstract
Monoamine oxidase-A knockout (MAO-A KO) mice have elevated brain serotonin (5-HT) and noradrenaline (NA) levels, and one would therefore anticipate increased monoamine release and compensatory changes in other aspects of presynaptic monoamine function. In this study we used voltammetry in brain slices from the locus coeruleus (LC), dorsal raphe (DRN) and striatum (CPu) in 7-week-old MAO-A KO and C3H control mice to measure stimulated monoamine efflux and its control by amine transporters and autoreceptors. In LC, peak NA efflux on stimulation (99 pulses, 100 Hz) was higher in MAO-A KO than C3H mice (938 ± 58 nm cf. 511 ± 42 nm; P < 0.001). The NA uptake half time (t½) was longer in MAO-A KO than in C3H mice (6.0 ± 0.9 s cf. 1.9 ± 0.3 s; P < 0.001) and the selective NA reuptake inhibitor desipramine (50 nm) had a smaller effect in MAO-A KO mice. NA transporter binding was significantly lower in the LC of MAO-A KO mice compared to C3H controls (P < 0.01) but not in the DRN. The α2 agonist dexmedetomidine (10 nm) decreased stimulated NA efflux more in C3H than in MAO-A KO mice (73.3% cf. 29.6% inhibition, P < 0.001). In DRN, peak 5-HT efflux on stimulation (99 pulses, 100 Hz) was greater (P < 0.01) in MAO-A KO (262 ± 44 nm) than C3H mice (157 ± 16 nm). Moreover, 5-HT uptake t½ was longer (P < 0.05) in MAO-A KO than in C3H mice (8.8 ± 1.1 s cf. 4.9 ± 0.6 s, P < 0.05) and the effect of citalopram (75 nm) was attenuated in MAO-A KOs. Serotonin transporter binding was also lower in both the DRN and LC of MAO-A KO mice. The 5-HT1A agonist 8-OH-DPAT (1 µm) decreased 5-HT efflux more in C3H than in MAO-A KO mice (38.3% inhibition cf. 21.6%, P < 0.001). In contrast, there were no significant differences between MAO-A KO and C3H mice in CPu dopamine efflux and uptake and the effect of the D2/3 agonist quinpirole was similar in the two strains. In summary, MAO-A KO mice show major dysregulation of monoaminergic presynaptic mechanisms such as autoreceptor control and transporter kinetics.