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In vivo effects of the 5-HT(6) antagonist SB-271046 on striatal and frontal cortex extracellular concentrations of noradrenaline, dopamine, 5-HT, glutamate and aspartate - PubMed

In vivo effects of the 5-HT(6) antagonist SB-271046 on striatal and frontal cortex extracellular concentrations of noradrenaline, dopamine, 5-HT, glutamate and aspartate

L A Dawson et al. Br J Pharmacol. 2000 May.

Abstract

Although the 5-HT(6) receptor subtype was identified some 5 years ago, very little is known about its function within the brain. Here we demonstrate, for the first time, the neurochemical effects of a selective 5-HT(6) receptor ligand. Using in vivo microdialysis in the freely moving rat, we evaluated the effects of the selective 5-HT(6) receptor antagonist SB-271046 by simultaneous measurement of 5-hydroxytryptamine (5-HT), dopamine (DA), noradrenaline (NA), glutamate and aspartate from the striatum and frontal cortex. SB-271046 did not alter basal levels of 5-HT, DA and NA in either brain region. Similarly, there was no change basal levels of either of the excitatory amino acids within the striatum. In contrast, administration of SB-271046 (10 mg kg(-1) s.c.) produced a significant (P<0.05), tetrodotoxin-dependent, increase in extracellular levels of both glutamate and aspartate within the frontal cortex, reaching maximum values of 375.4+/-82.3 and 215. 3+/-62.1% of preinjection values, respectively.

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Figures

Figure 1
Figure 1

Effects of SB-271046 (1 and 10 mg kg−1 s.c.) on frontal cortex extracellular levels of NA, DA and 5-HT. Data expressed as mean±s.e.mean, (n=7–12 per study group). Arrow denotes subcutaneous drug or vehicle injection points. Basal preinjection levels of neurotransmitter within the frontal cortex were: 5-HT–9.7±0.2, NA–11.1±0.2, DA–14.1±0.25 fmol per 20 l microdialysate (n=42).

Figure 2
Figure 2

Effects of SB-271046 (1 and 10 mg kg−1 s.c.) on frontal cortex extracellular levels of Glu and Asp. Data expressed as mean±s.e.mean, (n=7–12 per study group). Arrow denotes subcutaneous drug or vehicle injection points; solid bar denotes TTX or vehicle infusion. Basal preinjection levels of neurotransmitter within the frontal cortex were: and Glu–1.08±0.02, Asp–0.17±0.01 μ

M

(n=42).*Denotes statistical significance (P<0.05 ) from vehicle treated animals. **Denotes statistical significance (P<0.05) SB-271046 alone vs SB-271046+TTX treated animals.

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