5-HT1A Receptors In Rat Brain Research Articles

MicroPET imaging of 5-HT1A receptors in rat brain: a test–retest [18F]MPPF study

Earlier studies have shown that positron emission tomography (PET) imaging with the radioligand [(18)F]MPPF allows for measuring the binding potential of serotonin 5-hydroxytryptamine(1A) (5-HT(1A)) receptors in different regions of animal and human brain, including that of 5-HT(1A) autoreceptors in the raphe nuclei. In the present study, we sought to determine if such data could be obtained in rat, with a microPET (R4, Concorde Microsystems). Scans from isoflurane-anaesthetised rats (n = 18, including six test-retest) were co-registered with magnetic resonance imaging data, and binding potential, blood to plasma ratio and radiotracer efflux were estimated according to a simplified reference tissue model. Values of binding potential for hippocampus (1.2), entorhinal cortex (1.1), septum (1.1), medial prefrontal cortex (1.0), amygdala (0.8), raphe nuclei (0.6), paraventricular hypothalamic nucleus (0.5) and raphe obscurus (0.5) were comparable to those previously measured with PET in cats, non-human primates or humans. Test-retest variability was in the order of 10% in the larger brain regions (hippocampus, medial prefrontal and entorhinal cortex) and less than 20% in small nuclei such as the septum and the paraventricular hypothalamic, basolateral amygdaloid and raphe nuclei. MicroPET brain imaging of 5-HT(1A) receptors with [(18)F]MPPF thus represents a promising avenue for investigating 5-HT(1A) receptor function in rat.

Interaction of Orally Administered 5-{3-[((25)-1,4-Benzodioxan-2-ylmethyl)amino]propoxy}-1,3-benzodioxole (MKC-242) with 5-HT1A Receptors in Rat Brain

The present study was carried out to clarify whether orally administered 5-{3-[((25)-1,4-benzodioxan-2-ylmethyl)amino]propoxy}-l,3-benzodioxole (MKC-242), a serotonin1A (5-HTiA)-receptor agonist having potent anxiolytic-like and antidepressant-like effects in animal models, binds to 5-HTiA receptors in rat brain. Quantitative autoradiography showed that orally administered MKC-242 (0.1-0.5 mg/kg) caused a significant decrease in [3H]8-hydroxy-2-(di-h-propylamino)tetralin (8-OH-DPAT) binding in the hippocampus and dorsal raphe nucleus sections. The decrease in the binding by MKC-242 was observed up to 4 hr after administration, and the effective doses were similar to those in its anxiolytic-like effect in the animal models. Repeated treatment of MKC-242 (0.5 mg/kg/day, p.o.) or buspirone (30 mg/kg/day, p.o.) for 2 weeks did not affect [3H]8-OH-DPAT binding in both sections. These results suggest that orally administered MKC-242 at the low doses that do not show 5-HTiA-receptor-mediated in vivo responses such as the hypothermic effect, adrenocortical effect and the decrease in 5-HT turnover passes the blood-brain barrier and subsequently binds to 5-HT1A receptors in rat brain. In addition, they indicate that repeated stimulation of the receptors by the agonists does not affect the number of the binding sites.

3H]YM-09151-2 (nemonapride), a potent radioligand for both sigma 1 and sigma 2 receptor subtypes.

Using K+ phosphate buffer with 25 nM spiperone, [3H]YM-09151-2 binding showed a high affinity for sigma receptors but no affinity for D2 dopamine or 5-HT1A receptors in rat brain. The order of pKi values of various sigma compounds at [3H]YM-09151-2 binding sites and stereoisomer selectivity were consistent with previous studies using other sigma ligands such as (+)-[3H]SKF-10047, [3H]DTG and (+)-[3H]3-PPP. Although Scatchard analysis fitted a one-site model, competition between [3H]YM-09151-2 and (+)-pentazocine revealed two sites, sigma 1 and sigma 2 receptors, at which the Ki values of YM-09151-2 were 8.4 nM and 9.6nM, respectively. Autoradiography using [3H]YM-09151-2 also showed a characteristic distribution of sigma receptors in rat brain. [3H]YM-09151-2 is, therefore, a potent and useful radioligand for sigma 1/sigma 2 receptor subtypes.

O-022 - Anxiolytic effect of lisuride and its binding to 5-HT1A receptor in rat brain.

O-022 - Anxiolytic effect of lisuride and its binding to 5-HT1A receptor in rat brain.