Cortical [3H]ketanserin binding and 5-HT2A receptor-mediated inositol phosphate production in the spontaneously hypertensive rat and Lewis rat strains

doi:10.1016/S0304-3940(97)00716-7

Neuroscience Letters

Volume 236, Issue 2, 31 October 1997, Pages 112-116

https://doi.org/10.1016/S0304-3940(97)00716-7 Get rights and content

Abstract

The spontaneously hypertensive rat (SHR) and Lewis rat strains differ in the elevated plus-maze of anxiety, the former and the latter strain displaying low and high anxiety, respectively. A recent study has shown that serotonin (5-hydroxytryptamine, 5-HT)_2A receptor-mediated head shakes, but not [³H]ketanserin binding at these receptors, are less in Lewis rats, compared with SHRs. Herein, we have analysed the hypothesis of a difference in 5-HT_2A receptor-effector coupling between these two strains. Confirming our previous results, the B_max and K_D values for the specific [³H]ketanserin binding at cortical 5-HT_2A receptors were respectively identical in both strains. The accumulation of total inositol phosphates by the 5-HT_2A,2B,2C receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI; 0.01–100 μM) was concentration- and strain (Lewis>SHR)-dependent. Preincubation with 0.01 and 0.1 μM of the 5-HT_2A receptor antagonist SR 46349B, respectively, decreased and prevented DOI-elicited inositol phosphate production in both strains. The aforementioned genetic differences in 5-HT_2A receptor-mediated head shakes may thus lie at some point distal from the 5-HT_2A receptor.

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Acknowledgements

The authors wish to thank Sanofi Recherche (Montpellier, France) for the kind gift of SR 46349B, Dr. M. Allard (INSERM U378, Bordeaux, France) for allowing the use of the materials required for the estimation of phosphoinositide hydrolysis, and Dr. E. Sanders-Bush (Nashville, TN, USA) for comments on the phosphoinositide hydrolysis assay.

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[3H]-Ketanserin. The assays for [3H]-ketanserin binding were performed as previously described (Gauffre et al. 1997) with slight modifications. Briefly, the cerebral cortex were homogenized in 50 mM Tris–HCl buffer and centrifuged at 48,000 × g. Pellets were washed twice by resuspension in the same buffer followed by centrifugation at 48,000 × g.
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Cortical [3H]ketanserin binding and 5-HT2A receptor-mediated inositol phosphate production in the spontaneously hypertensive rat and Lewis rat strains

Abstract

Section snippets

Acknowledgements

Trends Pharmacol. Sci.

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Methods Neurosci.

Neuropharmacology

Pharmacol. Ther.

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Mol. Brain Res.

Behav. Brain Res.

Cortical [³H]ketanserin binding and 5-HT_2A receptor-mediated inositol phosphate production in the spontaneously hypertensive rat and Lewis rat strains