Central serotonin1A receptors: Respective distributions of encoding mRNA, receptor protein and binding sites by in situ hybridization histochemistry, radioimmunohistochemistry and autoradiographic mapping in the rat brain

Miquel, Marie‐Christine; Doucet, Édith; Boni, Claudette; Mestikawy, Salah El; Matthiessen, Line; Daval, G.; Vergé, Daniel; Hamon, Michel

doi:10.1016/0197-0186(91)90063-j

Cited by 108 publications

(44 citation statements)

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“…These fibres project to the stratum radiatum of the hippocampus proper, weakly into the stratum oriens, and to the polymorphic cell layer of the dentate gyrus (Azmitia & Segal, 1978;Oleskevich & Descarries, 1990). This innervation conforms well to the 5-HTIA receptor distribution in the CAl area and the dentate gyrus as assessed by mRNA expression and receptor binding studies (Miquel et al, 1991). These receptors are mainly located on dendritic projections of pyramidal and granule neurones (Pompeiano et al, 1992).…”

Section: Discussionmentioning

confidence: 85%

Stimulation of 5‐HT_1A receptors in the dorsal hippocampus and inhibition of limbic seizures induced by kainic acid in rats

Gariboldi

Tutka

Samanin

et al. 1996

British J Pharmacology

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Section: Discussionmentioning

confidence: 85%

Stimulation of 5‐HT_1A receptors in the dorsal hippocampus and inhibition of limbic seizures induced by kainic acid in rats

Gariboldi

Tutka

Samanin

et al. 1996

British J Pharmacology

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“…1). Both radioligands displayed a pattern of binding typical of the 5-HT1A receptors, with highest densities in the hippocampus, dorsal raphe, interpeduncular nucleus, and lateral septum (14). No specific binding was found in knockouts with either ligand (Fig.…”

Section: Resultsmentioning

confidence: 99%

Serotonin receptor 1A knockout: An animal model of anxiety-related disorder

Ramboz

Oosting

Amara

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

741

487

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To investigate the contribution of individual serotonin (5-hydroxytryptamine; 5-HT) receptors to mood control, we have used homologous recombination to generate mice lacking specific serotonergic receptor subtypes. In the present report, we demonstrate that mice without 5-HT1A receptors display decreased exploratory activity and increased fear of aversive environments (open or elevated spaces). 5-HT1A knockout mice also exhibited a decreased immobility in the forced swim test, an effect commonly associated with antidepressant treatment. The serotonin (5-hydroxytryptamine; 5-HT) receptor 1A is found on serotonergic neurons, where it acts as an autoreceptor, and on nonserotonergic neurons (1). 5-HT1A receptor agonists are currently used in the treatment of anxiety disorders (2), and antagonists of this receptor have been suggested to improve the efficacy of certain antidepressant drugs (3). However, the clinical value of these drugs, as well as their mechanism of action, is still unclear. To study the role of the 5-HT1A receptor in mood control, we have generated mice lacking this receptor by homologous recombination (see Methods). The disruption of the 5-HT1A receptor gene was verified by Southern blot analysis (not shown). Despite suggestions that 5-HT1A receptors play a role in development (4, 5), these knockout mice had normal growth and viability and did not display any obvious anatomical or behavioral abnormalities. MATERIALS AND METHODS5-HT1A Gene Targeting. The 5-HT1A gene was cloned from a 129͞Sv mouse genomic library (Lambda EMBL3, Stratagene) by using the human 5-HT1A gene as a probe (6). A KpnI fragment containing the 5-HT1A gene was cloned in pGEM-13(ϩ). The PGK-neo gene was inserted into an AscI site located after the third transmembrane domain of the 5-HT1A gene. W9.5 embryonic stem cells were electroporated (Bio-Rad Gene Pulser; 800 V and 3 F) with 30 g of the targeting construct. These embryonic stem cells were then plated onto mitomycin treated mouse embryonic fibroblasts for 1 week in the presence of G418 (150 g per ml of active substance). The G418-resistant clones were screened by Southern blot with a BglII digest and a 32 P-labeled outside probe (600-bp HindIII-KpnI fragment). Positive cells for the targeting event were injected into C57BL6͞J blastocysts. These blastocysts were reimplanted in B6CBAF1͞J foster mothers, which gave birth to chimeric mice. Chimeras were mated with 129͞Sv females to generate heterozygous mutant (ϩ͞Ϫ) mice on a pure 129͞Sv genetic background. The resulting heterozygous mice were bred and generated 25% homozygous mutant mice.Autoradiography Studies. Coronal cryostat sections (20 m) from three brains of adult male mice were thaw-mounted on gelatin-coated slides and stored at Ϫ20°C. 8-Hydroxy-2-(di-n-[ 3

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“…The site(s) at which 5-HT 1A receptors control DA neuron activity is still a matter of debate. A direct effect on DA cell bodies seems to be excluded as neither 5-HT 1A receptor protein nor mRNA have been detected in the VTA and SN (Miquel et al, 1991). Moreover, since DA efflux was evoked by electrical stimulation of the ascending dopaminergic pathway, activation of 5-HT 1A autoreceptors present on DRN neurons afferent to the VTA cannot be invoked.…”

Section: Mesocorticolimbic Selectivity and Atypical Antipsychotic Promentioning

confidence: 95%

SSR181507, A Dopamine D2 Receptor Antagonist and 5-HT1A Receptor Agonist. I: Neurochemical and Electrophysiological Profile

Claustre

Peretti

Brun

et al. 2003

Neuropsychopharmacol

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monohydrochloride) is a novel tropanemethanamine benzodioxane derivative that possesses high and selective affinities for D2-like and 5-HT 1A receptors (K I ¼ 0.8, 0.2, and 0.2 nM for human D 2 , D 3 , and 5-HT 1A , respectively). In vivo, SSR181507 inhibited [ 3 H]raclopride binding to D 2 receptors in the rat (ID 50 ¼ 0.9 and 1 mg/kg, i.p. in limbic system and striatum, respectively). It displayed D 2 antagonist and 5-HT 1A agonist properties in the same concentration range in vitro (IC 50 ¼ 5.3 nM and EC 50 ¼ 2.3 nM, respectively, in the GTPgS model) and in the same dose range in vivo (ED 50 ¼ 1.6 and 0.7 mg/kg, i.p. on striatal DA and 5-HT synthesis, respectively, and 0.03-0.3 mg/kg, i.v. on dorsal raphe nucleus firing rate). It selectively enhanced Fos immunoreactivity in mesocorticolimbic areas as compared to the striatum. This regional selectivity was confirmed in electrophysiological studies where SSR181507, given acutely (0.1-3 mg/kg, i.p.) or chronically (3 mg/kg, i.p., o.d., 22 days), increased or decreased, respectively, the number of spontaneous active DA cells in the ventral tegmental area, but not in the substantia nigra. Moreover, SSR181507 increased both basal and phasic DA efflux (as assessed by microdialysis and electrochemistry) in the medial prefrontal cortex and nucleus accumbens, but not in the striatum. This study shows that the combination of D 2 receptor antagonism and 5-HT 1A agonism, in the same dose range, confers on SSR181507 a unique neurochemical and electrophysiological profile and suggests the potential of this compound for the treatment of the main dimensions of schizophrenia.

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Central serotonin1A receptors: Respective distributions of encoding mRNA, receptor protein and binding sites by in situ hybridization histochemistry, radioimmunohistochemistry and autoradiographic mapping in the rat brain

Cited by 108 publications

References 20 publications

Stimulation of 5‐HT_1A receptors in the dorsal hippocampus and inhibition of limbic seizures induced by kainic acid in rats

Stimulation of 5‐HT_1A receptors in the dorsal hippocampus and inhibition of limbic seizures induced by kainic acid in rats

Serotonin receptor 1A knockout: An animal model of anxiety-related disorder

SSR181507, A Dopamine D2 Receptor Antagonist and 5-HT1A Receptor Agonist. I: Neurochemical and Electrophysiological Profile

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Central serotonin1A receptors: Respective distributions of encoding mRNA, receptor protein and binding sites by in situ hybridization histochemistry, radioimmunohistochemistry and autoradiographic mapping in the rat brain

Cited by 108 publications

References 20 publications

Stimulation of 5‐HT1A receptors in the dorsal hippocampus and inhibition of limbic seizures induced by kainic acid in rats

Stimulation of 5‐HT1A receptors in the dorsal hippocampus and inhibition of limbic seizures induced by kainic acid in rats

Serotonin receptor 1A knockout: An animal model of anxiety-related disorder

SSR181507, A Dopamine D2 Receptor Antagonist and 5-HT1A Receptor Agonist. I: Neurochemical and Electrophysiological Profile

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Stimulation of 5‐HT_1A receptors in the dorsal hippocampus and inhibition of limbic seizures induced by kainic acid in rats

Stimulation of 5‐HT_1A receptors in the dorsal hippocampus and inhibition of limbic seizures induced by kainic acid in rats