Reconsideration of 5-Hydroxytryptamine (5-HT)₇Receptor Distribution Using [³H]5-Carboxamidotryptamine and [³H]8-Hydroxy-2-(di-n-propylamino)tetraline: Analysis in Brain of 5-HT_1AKnockout and 5-HT_1A/1BDouble-Knockout Mice

Abstract

The characterization and anatomical distribution of 5-hydroxytryptamine (5-HT) 7 receptor binding sites in brain tissue has been hampered by the lack of a specific radioligand. In the present autoradiographic study, we took advantage of 5-HT 1A knockout and 5-HT 1A/1B double-knockout mice to revisit the pharmacological characterization and anatomical localization of 5-HT 7 binding sites in mouse brain using [ The 5-HT 7 receptor is the most recently identified member of the family of G protein-coupled 5-HT receptors (for review, see Vanhoenacker et al., 2000). The 5-HT 7 receptor has been cloned from rat Ruat et al., 1993;Shen et al., 1993), mouse (Plassat et al., 1993), human (Bard et al., 1993), and guinea pig (Tsou et al., 1994). The receptor is positively coupled to adenylate cyclase, preferentially via Gs. It exhibits a high degree of interspecies homology (approximately 95%) but a low sequence homology with other 5-HT receptors (Ͻ40%). In rat and human, three different splice variants have been described to date, which are thought to have similar pharmacology and function (Heidmann et al., 1997;Krobert et al., 2001). The pharmacological profile of the 5-HT 7 receptor is consistent across all tested species and is characterized by high affinity for the 5-HT 1 agonists 5-CT, 5-HT, and 8-OH-DPAT; and the 5-HT 2 antagonists ritanserin, metergoline, mesulergine, and risperidone. Possible physiological functions for this receptor have been suggested, including relaxation in several vascular preparations (Bard et al., 1993;Shen et al., 1993) and circadian rhythm control via the suprachiasmatic nucleus of the hypothalamus Gannon, 2001). Because 8-OH-DPAT has been shown to exhibit a relatively high affinity for the 5-HT 7 receptor, multiple functions formerly ABBREVIATIONS:

Distribution of serotonin 5-HT 1A -binding sites in the brainstem and the hypothalamus, and their roles in 5-HT-induced sleep and ingestive behaviors in rock pigeons ( Columba livia )

“…To avoid the binding of [ 3 H]-8-OH-DPAT to 5-HT 7Rs , we used a concentration that does not bind to 5-HT 7Rs in 5-HT 1AR knockout mice. Bonaventure and colleagues [69] demonstrated that 1 or 2 nmol [ 3 H]-8-OH-DPAT does not bind or displays a very low binding density in the septal area of knockout mice compared to the moderate to high binding densities in the area of wild-type animals [69]. Consistently, lower K D values (1.3 nM, 95% confidence interval 0.35-2.25 nM) were obtained in the septum of wild-type animals than in that of knockout animals (5-HT 1AR knockout animals: 20 nM, 95% confidence interval 14-27 nM).…”

Heterodimerization of serotonin receptors 5-HT1A and 5-HT7 differentially regulates receptor signalling and trafficking

“…This is supported by several observations. First, analysis of the brain regional distribution of 5-HT 7 receptor has revealed that this receptor is highly enriched in serotonergic neurons of dorsal raphe nuclei in adults (Neumaier et al, 2001;Bonaventure et al, 2002;Martín-Cora and Pazos, 2004). Together with the finding that the 5-HT 1A receptor has a higher affinity for forming heterodimeric (5-HT 1A -5-HT 7 ) rather than homodimeric (5-HT 1A -5-HT 1A ) complexes, this suggests that serotonergic neurons in raphe nuclei express a relative high level of heterodimers, i.e.…”

Role of the 5-HT7 Receptor in the Central Nervous System: from Current Status to Future Perspectives

“…However, a lack of impairment in the spatial Barnes maze task suggests that the 5-HT7 receptor is not critical for place learning in general [69]. In order to detect possible neuronal mechanisms underlying the observed learning deficit, Roberts et al studied synaptic plasticity within the CA1 region of the hippocampus, which is known to contain 5-HT7 receptorbinding sites [161]. Using paired pulse facilitation and paired pulse inhibition, it was observed that short-term plasticity was not altered in the 5-HT7 −/− mice.…”