Biomedical subjects

G Fillion

Publications and source records attributed to G Fillion.

At least 37 records · Page 2Linked to original sources

PubMed1998

Mapping of 5-HT-moduline binding sites in guinea-pig brain by film and digital autoradiography.

5-HT-moduline is a cerebral tetrapeptide [Leu-Ser-Ala-Leu] that was recently isolated from bovine brain tissue and shown to interact specifically with 5-HT1B receptors, particularly in rodents. The pharmacological properties of 5-HT1B receptors in rodents are different from those in other species. In order to better understand the role of this peptide in non-rodent species, we determined the distribution of 5-HT-moduline binding sites in guinea-pig brain using both the film autoradiography and digital autoradiography with a newly developed high resolution beta-imaging techniques. We found that 5-HT-moduline binding sites were expressed in various brain regions. Quantitative analysis showed that densities of binding sites were similar to those observed previously in rat brain. Regions with the highest labelling included cortex, septum, hippocampus and some regions of basal ganglia. Our results extend previous data and show that 5-HT-moduline interacts with the two forms of 5-HT1B receptors that are distinct pharmacologically. By this interaction, 5-HT-moduline may play an important role in regulating the functional activity of 5-HT1B receptors, thereby contributes to the pathophysiology of serotonergic transmission.

Animals↗

PubMed1998

Characterization of 5-ht6 receptor and expression of 5-ht6 mRNA in the rat brain during ontogenetic development.

We have determined the pharmacological characteristics of the rat 5-ht6 receptor stably expressed in CHO cells. Moreover, using RT-PCR experiments the in vivo expression of the gene encoding this receptor was studied in rat at various embryonic days (ED) starting from ED10 to birth (PN0) and at post-natal days (PN) up to PN36. The pharmacological analysis of the [3H]5-HT binding in stably transfected CHO cells expressing rat 5-ht6 receptors revealed the presence of a single class of high affinity saturable binding sites for 5-HT corresponding to an affinity constant: Kd=27.2+/-3.4 nM. This receptor also exhibited a high affinity for a number of typical and atypical antipsychotics, tricyclic antidepressant drugs and ergot alkaloïds. In stably transfected CHO cells, serotonin elicited a potent stimulation of adenylyl cyclase activity which was blocked by antipsychotic and antidepressant drugs. These results confirm the hypothesis that 5-ht6 receptors may correspond to an important target for atypical antipsychotics and reveal an original pharmacological profile for this receptor. The study of the ontogeny of the 5-ht6 mRNA in rat developing brain showed that 5-ht6 mRNA were first detectable with a high level on ED12, slighly decreased up to ED17 and then remained stable at high level until the adult age. The ontogenetic pattern of 5-ht6 mRNA expression appeared to correlate with the occurence of the first cell bodies of serotonergic neurons; the early expression of 5-ht6 mRNA and the fact that this receptor is positively coupled to the production of cAMP may suggest a role for 5-ht6 receptor in the early growth process involving the serotonergic system.

Adenylyl Cyclases↗

PubMed1998

Specific interaction of 5-HT-moduline with human 5-HT1b as well as 5-HT1d receptors expressed in transfected cultured cells.

5-HT1B receptors are the predominant auto- and heteroreceptors located on serotonergic and non-serotonergic terminals where they regulate the neuronal release of neurotransmitters. 5-HT-moduline (Leu-Ser-Ala-Leu) has been shown to specifically interact with a very high apparent affinity and in a non-competitive manner with 5-HT1B receptors (Massot et al. 1996; Rousselle et al. 1996). Using transfected cells expressing either 5-HT1B or 5-HT1D receptors, it was shown that 5-HT-moduline prevents the binding of [3H]5-HT to 5-HT1B as well as to 5-HT1D receptors with similar biochemical characteristics: the IC50 of the peptide was 1.2x10(-12) M for 5-HT1B and 9x10(-13) M for 5-HT1D receptors. The observed effect corresponds to a marked decrease of the maximal binding for [3H]5-HT on 5-HT1B (-51.2 +/- 1%) as well as 5-HT1D binding (-47.2 +/- 7.7% of the control binding) whereas the affinity of 5-HT is increased by a factor close to 3. No effect is observed using the "scrambled" peptide (Ala-Leu-Leu-Ser). Parallel assays using transfected cells expressing 5-HT1A or 5-ht6 receptors did not show any significant change induced by the peptide under similar assay conditions. The interaction of the peptide was also studied on the functional activity related to the stimulation of the receptors as measured by the increase in [35S]GTPgammaS binding reflecting the coupling of the receptor to the G-protein. 5-HT-moduline yields an antagonistic effect on the 5-HT induced coupling with a corresponding IC50 = 1.2 +/- 0.7x10(-12) M for 5-HT1B and 9.8 +/- 4.0x10(-12) M for 5-HT1D receptors, respectively. The present results demonstrate that 5-HT-moduline interacts with 5-HT1D as well as 5-HT1B receptors and possesses a non-competitive antagonistic activity, likely corresponding to its role of endogenous allosteric modulator, specific for both 5-HT1B and 5-HT1D receptors.

Allosteric Regulation↗

PubMed1998

Effects of moderate and intensive training on functional activity of central 5-HT1B receptors in the rat substantia nigra.

The efficacy of the selective 5-HT1B receptor agonist CP 93,129 in inhibiting the forskolin-stimulated adenylyl cyclase activity in the rat substantia nigra was reduced by both moderate and intensive prolonged training compared with sedentary resting rats. The concentration-response curves of the agonist were shifted to the right with a sixfold increase of the half-maximal inhibitory concentration. A difference was observed between the two training exercises in regard to further changes in 5-HT1B receptor sensitivity induced by an acute restraint stress. This manipulation did not affect the functional response of the 5-HT1B receptors further in moderately trained rats, whereas an additional desensitization of the 5-HT1B receptors was observed in intensively trained rats. These results strongly suggest the existence of regulation mechanisms altering the functional efficacy of 5-HT1B receptors and, accordingly, affecting the serotonergic activity, since 5-HT1B receptors modulate the neuronal release of the amine.

Adenylyl Cyclases↗

PubMed1998

Pasteur Euroconference on future therapies for an anxious world.

The aim of this meeting was to explore the molecular targets for tomorrow's drugs with a group of European and North American speakers from the pharmaceutical industry and academia presenting both data and ideas. Several speakers considered 5-hydroxytryptamine(1B/D) (5-HT(1B/D)) receptor antagonists to be a promising target for the treatment of obsessive compulsive disorders (OCD). 5-HT moduline, a peptide modulator of the 5-HT(1B/D) receptor, presents a potentially subtle way of intervention. No clinical data are as yet available on 5-HT(1B/D) receptor antagonists. The paradox of agonists, partial agonists and antagonists at the 5-HT(1A) receptor (all having anxiolytic activity in animal models) was discussed. Although the 5-HT(1A) agonists tested in clinical trials to date have been disappointing, the clinical potential of 5-HT(1A) antagonists still has to be evaluated. Similarly, both agonists and antagonists at the 5-HT(2C) receptor have been shown to be active in animal models of anxiety. It seems, however, that 5-HT(2C) agonists may have a therapeutic potential in panic disorders and OCD, while the antagonists may be more appropriate in generalised anxiety. Cholecystokinin (CCK) has been shown to be implicated in panic attacks which can be induced by agonists at the CCK-B subtype. CCK-B antagonists are thus potential antipanic agents although this has not yet been confirmed by clinical trials. Finally, inhibition of glutamatergic neurotransmission produces anxiolytic effects in a wide-range of animal models and the new antagonists at the metabotropic glutamate receptors may have potential as anti-anxiety agents. This report focuses on the presentations that addressed novel drug candidates or potential new drug targets.

Journal Article↗

PubMed1998

[5HT-moduline an new peptide specifically interactive with the serotonergic system: physiopathologic implications].

5-HT1B receptors play a specific role as one of the many receptors regulating serotonergic activity. This endogenous peptide was recently isolated and characterized. Specific interaction has been demonstrated. 5-HT-moduline appears to be implicated in central nervous system response to various stimuli, particularly stress. It might play an important role in adaptation/inadaptation mechanisms (stress, anxiety, depression).

Animals↗

PubMed1997

Autoradiographic characterization of [3H]-5-HT-moduline binding sites in rodent brain and their relationship to 5-HT1B receptors.

5-HT-moduline is an endogenous tetrapeptide [Leu-Ser-Ala-Leu (LSAL)] that was first isolated from bovine brain tissue. To understand the physiological role of this tetrapeptide, we studied the localization of 5-HT-moduline binding sites in rat and mouse brains. Quantitative data obtained with a gaseous detector of beta-particles (beta-imager) indicated that [3H]-5-HT-moduline bound specifically to rat brain sections with high affinity (Kd = 0.77 nM and Bmax = 0. 26 dpm/mm2). Using film autoradiography in parallel, we found that 5-HT-moduline binding sites were expressed in a variety of rat and mouse brain structures. In 5-HT1B receptor knock-out mice, the specific binding of [3H]-5-HT-moduline was not different from background labeling, indicating that 5-HT-moduline targets are exclusively located on the 5-HT1B receptors. Although the distribution of 5-HT-moduline binding sites was similar to that of 5-HT1B receptors, they did not overlap totally. Differences in distribution patterns were found in regions containing either high levels of 5-HT1B receptors such as globus pallidus and subiculum that were poorly labeled or in other regions such as dentate gyrus of hippocampus and cortex where the relative density of 5-HT-moduline binding sites was higher than that of 5-HT1B receptors. In conclusion, our data, based on autoradiographic localization, indicate that 5-HT-moduline targets are located on 5-HT1B receptors present both on 5-HT afferents and postsynaptic neurons. By interacting specifically with 5-HT1B receptors, this tetrapeptide may play a pivotal role in pathological states such as stress that involves the dysfunction of 5-HT neurotransmission.

Animals↗

PubMed1997

Immunocytochemical localization of neurons expressing 5-HT-moduline in the mouse brain.

The localization of 5-HT-moduline, an endogenous cerebral tetrapeptide (LSAL) which specifically interacts with 5-HT1B receptors (Rousselle et al., 1996; Massot et al., 1996) was examined in mouse brain using an immunocytochemistry technique with a polyclonal anti-peptide antibody highly specific for this tetrapeptide. Highest levels of 5-HT-moduline immunoreactivity were observed in the cerebral cortex including cingulate, retrosplenial, parietal and pyriform cortical areas and in the basal ganglia. Intense immunoreactivity also occurred in the hippocampus, subiculum, various hypothalamic and thalamic nuclei and in some midbrain regions such as the substantia nigra and the superior colliculi. Immunoreactive neurons generally showed intense and extensive labelling of the perikarya and dendritic arborizations with moderate to heavy characteristic deposits of reaction product along plasma membranes and within cytoplasm while the nuclei were devoid of reaction product. The results obtained indicated that 5-HT-moduline immunoreactivity was heterogenously distributed in neuronal structures of mouse brain. The distribution of 5-HT-moduline immunoreactivity closely correlated with that of 5-HT-moduline specific binding sites as visualized by autoradiography (Massot et al., 1996). Moreover, it seems to overlap with the distribution of serotonergic innervation and also with that of 5-HT1B receptors in mouse brain (Boschert et al., 1994; Bruinvels et al., 1994; Chopin et al., 1994; Langlois et al., 1995). These data provide evidence that 5-HT-moduline immunoreactivity is located in cells with the morphological appearance of neurones. Its localization in brain areas which also contain 5-HT1B receptors, is in good agreement with previous demonstrations that this peptide specifically interacts with 5-HT1B receptors to regulate their functional activity and accordingly controls the modulatory activity of the serotoninergic system on various CNS functions.

Animals↗

PubMed1997

The endogenous cerebral tetrapeptide 5-HT-moduline reduces in vivo the functional activity of central 5-HT1B receptors in the rat.

5-HT-moduline (Leu-Ser-Ala-Leu, LSAL) is a novel endogenous peptide isolated from rat brain which interacts in vitro specifically with 5-HT(1B) receptors by a non-competitive mechanism. In the present study, we demonstrate that the efficacy of the selective 5-HT(1B) receptor agonist CP 93 129 in inhibiting the forskolin-stimulated adenylyl cyclase activity in the rat substantia nigra was reduced 15 min after intracerebral injection of LSAL compared to vehicle or ALLS (scrambled peptide) injected rats. Accordingly, the concentration-response curve of the agonist is shifted to the right with a 3.5-fold increase of the half-maximal inhibitory concentration compared to vehicle injected rats. Thus, the in vivo desensitization of serotonergic autoreceptors strongly strengthens the important role of 5-HT-moduline in the rapid adaptative control of the serotonergic system, implicated in numerous pathological events as anxiety and depression.

Animals↗

PubMed1997

Analysis of brain mRNA by reverse transcription-polymerase chain reaction and hybridization with digoxigenin-labeled DNA probe.

The interleukin-1 family of polypeptides (IL-1 alpha, IL-1 beta and IL-1 receptor antagonist (RA)) induces various centrally mediated host defense responses to infectious pathogens. Considerable interest has focussed on IL-1 as a mediator in disease and in the production of systemic acute phase responses. We have recently studied the effects of a peripheral stimulation by intraperitoneal (i.p.) administration of lipopolysaccharide (LPS) on the mRNAs expressions of IL-1 (alpha, beta, RA) and their receptors (IL-1 receptor type I and type II (IL-1R1, IL-1R2)) in the central nervous system (CNS). The levels of these expressions being very low in the CNS, the reverse transcription-polymerase chain reaction (RT-PCR) techniques are required for these studies. RT-PCR is a developed method of identifying mRNAs in very small amount of nucleic acid. We have previously developed a method to choose specific PCR primers. The detection of specific PCR products is extremely important. Since amplifications with these specific PCR primers can be achieved under the same conditions (buffers and temperatures) reliable results can be obtained. Characterization of a PCR product requires the use of a specific DNA probe that hybridizes to the region of interest. In addition to providing specificity of detection, the use of labeled DNA probes provides increased sensitivity over ethidium bromide staining. We have previously described a method of synthesis of non-radioactive probe labeled with digoxigenin by nested PCR. Moreover the major advantage to the use of non-radioactive label is that it does not have a short half-life and can last for weeks or even months. A quantification of the PCR products can be obtained using a method based on the analysis of photographic negatives of agarose gels.

Animals↗

PubMed1997

The in situ hybridization and immunocytochemistry techniques for characterization of cells expressing specific mRNAs in paraffin-embedded brains.

In situ hybridization (ISH) represents a powerful and sensitive method for examining gene expression in individual cells in a manner analogous to immunocytochemistry (ICC) which is used to localize and identify cells containing a particular protein or labile antigens such as amino acid neurotransmitters. Considerable progress has been made both in molecular cloning which provides nucleotide probes and in the production of antibodies to specific antigens, especially those directed against small haptenes such as GABA and catecholamines. Consequently, specific tools have become available for ISH and ICC procedures in most cases. Several techniques including double ISH, double ICC and ISH coupled to ICC have been developed to characterize the phenotype of cells expressing neurotransmitters or specific neuroreceptors. This has been particularly well illustrated for neuropeptides (Young, III, W.S., Mezey, E. and Siegel, R.E. Vasopressin and oxytocin mRNAs in adrenalectomized and Brattleboro rats: analysis by quantitative in situ hybridization and histochemistry, Mol. Brain Res., 1 (1986) 231-241[17]) or dopamine receptors (Le Moine, C., Normand, E., Guitteny, A.F., Fouque, B., Teoule, R. and Bloch, B., Dopamine receptor gene expression by enkephalin neurons in rat forebrain, Proc. Natl. Acad. Sci. (USA), 87 (1990) 20-24 [8]; Le Moine, C., Normand, E. and Bloch, B., Phenotypical characterisation of the rat striatal neurons expressing the D1 dopamine receptor gene, Proc. Natl. Acad. Sci. (USA), 88 (1991) 4205-4209 [9]) but exclusively on frozen tissues. Combination of ISH and ICC allows the simultaneous detection of specific mRNAs and antigens in a same section or in adjacent sections. However, when ISH is coupled to ICC on a same section, a loss of signal in ISH is often observed (Siegel, R.E., Localization of neuronal mRNAs by hydridization histochemistry. In: P.M. Conn (Ed.), Methods in Neurosciences. Gene Probes. Vol. 1, Academic Press, New York, 1989, pp. 136-150 [13]) which may be a handicap when the rate of mRNA expression is low. Moreover, interferences between ISH coupled to ICC techniques may occur leading to artifactual signals. In the present protocol, in situ hybridization with a specific 35S-labeled riboprobe and immunocytochemistry with a polyclonal antibody are performed on adjacent sections of paraffin-embedded rodent brains. Paraffin embedding allows a better preservation of tissue morphology than freezing procedure. This is of particular importance since simultaneous detection of mRNAs and proteins in the same cell populations on adjacent sections requires conditions where (a) cell morphology is highly retained in a same manner on adjacent sections, and (b) reactivity of nucleic acids and antigens is preserved. We have used this technique to analyze the presence of serotonin 5-HT(1B) mRNA in GABAergic cell bodies (Cloëz-Tayarani, I., Wusher, N., Huerre, M. and Fillion, G., Cellular localization of 5-HT(1B) receptor mRNA in the rat olfactory tubercle: do GABAergic neurons express the 5-HT(1B) gene? Mol. Brain Res., 36 (1996) 337-342 [3]).

Animals↗

PubMed1997

Autoradiographic localization of 5-HT1E and 5-HT1F binding sites in rat brain: effect of serotonergic lesioning.

5-carboxamidotryptamine (5-CT)-insensitive binding sites labelled by [3H]5-hydroxytryptamine (5-HT) in the presence of 100 nM 5-CT and 100 nM mesulergine, were examined by semi-quantitative autoradiography in rat brain. Under these conditions most of the labelled sites correspond to 5-HT1E and 5-HT1F sites. The 5-CT-insensitive binding is located mainly in cortical layer V, caudate-putamen, interpeduncular nucleus and claustrum. In cortex and caudate-putamen, a large proportion of 5-CT-insensitive sites is displaced by 250 nM sumatriptan and can be attributed to the presence of 5-HT1F receptors. A low, but significant, level of displacement by sumatriptan was observed in the choroid plexus. Lesions of serotonergic neurones by intracerebroventricular 5,7-dihydroxytryptamine injection does not significantly modify the densities of 5-HT1E or 5-HT1F binding sites. Our findings suggest that the 5-HT1F receptor has a limited distribution in rat brain, mainly located on non-serotonergic neurones.

Animals↗

PubMed1996

Expression of serotonin receptors in human fetal astrocytes and glioma cell lines: a possible role in glioma cell proliferation and migration.

Expression of seven serotonin or 5-hydroxytryptamine (5-HT) receptors (5-HT1D alpha, 5-HT1E, 5-HT2, 5-HT1A, 5-HT1C, 5-HT1D beta, and 5-HT6) was investigated in human normal fetal astrocytes and eight glioma cell lines by reverse transcription and polymerase chain reaction (RT-PCR). No expression of 5-HT1D beta and 5-HT6 was observed in any of the cell lines studied. The 5-HT1D alpha receptor was found to be expressed in two human glioma cell lines but not in normal astrocytes. In addition, only three glioma cell lines expressed the 5-HT1E receptor. The 5-HT1C receptor was expressed in six glioma cell lines but not in normal astrocytes while the 5-HT1A was found to be expressed in normal astrocytes from the left hemisphere and in six glioma cell lines but not in normal astrocytes from the cerebellum. Interestingly, the 5-HT2 receptor was expressed in all cells studied but very weakly in normal astrocytes. The effect of 5-HT on glioma cell proliferation, migration, and invasion was also investigated. Serotonin was found to positively modulate these three processes in vitro. These results suggest that 5-HT may play an important role in the control of the biological properties of human glioma cells.

Astrocytes↗

PubMed1996

Sub-chronic cold stress reduces 5-HT1A receptor responsiveness in the old but not in the young rat.

The inhibitory effect of the prototypical 5-hydroxytryptamine (5-HT)1A receptor agonist 8-hydroxy-2-(di-n-propyl amino)tetraline (8-OH-DPAT) on forskolin-stimulated adenylyl cyclase activity, has been examined as an index of the functional activity of 5-HT1A receptors in the hippocampus of young (3 months) and old (18 months) rats exposed during 24 h or 5 days to cold. In both young and old rats exposed to cold stress during 24 h, there was a reduction in the potency (EC50) and/or the maximal inhibitory effect (Emax) of 8-OH-DPAT in reducing forskolin-induced cAMP accumulation. The properties of the hippocampal 5-HT1A sites labelled by [3H]8-OH-DPAT were not affected by these stressful conditions. Moreover, while the sensitivity of 5-HT1A receptors to 8-OH-DPAT in young rats returned to control values after 5 days of cold exposure, old rats still exhibited a significant desensitization of 5-HT1A receptors as compared to naive animals. These results point out the capacity of young but not of old rats to adapt to the aversive effects of a subchronic stressor.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed1996

Isolation and characterization of an endogenous peptide from rat brain interacting specifically with the serotonergic 1B receptor subtypes.

The existence of endogenous compounds interacting with the serotonergic system was previously postulated. In the present work, rat brain tissues were extracted by acidic and organic procedures. The resulting extract was tested for its capacity to interact with the binding of [3H]5-hydroxytryptamine ([3H]5-HT) to 5-HT1 receptors. Compounds responsible for the observed inhibitory activities were isolated and purified by high pressure liquid chromatography. A tetrapeptide corresponding to a novel amino acid sequence Leu-Ser-Ala-Leu (LSAL) was identified. It reduces the binding of [3H]5-HT to 5-HT1 receptors at low concentration (IC50 = 10(-10) M). This effect corresponds to a specific interaction at 5-HT1B receptors since LSAL does not significantly affect other neurotransmitter bindings. LSAL appears heterogeneously distributed throughout the brain (hippocampus > cerebellum > striatum > brain stem) and in peripheral tissues (kidney > lung > stomach > blood > liver > spleen). Two other peptides, Leu-Ser (LS) and Ala-Leu (AL), were also purified. They hardly affected [3H]5-HT binding compared with LSAL. They presumably represent degradation products of the functional peptide LSAL. The fact that LSAL interacts specifically with 5-HT1B receptors that inhibit the release of neurotransmitters and particularly that of 5-HT itself suggests that this peptide may be involved in mechanisms controlling 5-HT neurotransmission and, accordingly, may play an important role in pathophysiological functions related to 5-HT activity.

Amino Acid Sequence↗

PubMed1996

Interleukin-1 receptors type I and type II in the mouse brain: kinetics of mRNA expressions after peripheral administration of bacterial lipopolysaccharide.

The expression of transcripts for Interleukin-1 (IL-1) type I and type II receptors (IL-1R1, IL-1R2) was investigated in the mouse brain and spleen using reverse transcription-polymerase chain reaction techniques under basal conditions and following injection of endotoxin (LPS, i.p., 4 mg/kg). Under basal conditions, mRNAs for both receptor types were found in various parts of the brain, in pituitary as well as in spleen. Following LPS stimulation, mRNA expressions were increased in all studied tissues. IL-1R1 mRNAs were predominant in the brain and pituitary while, IL-1R2 mRNAs were more abundant in the spleen. The maximal quantity of transcripts (IL-1R1, IL-1R2) was obtained 6 h after LPS injection in all studied tissues. The decrease to basal level was observed within 48 h in the brain. In the spleen, IL-1R1 mRNAs remained elevated 48 h after LPS while IL-1R2 mRNAs had already reached basal level. These results indicate a LPS-induced stimulation of IL-1 receptors mRNAs in the brain and a differential expression of IL-1R1 and IL-1R2 transcripts in brain and immune tissues.

Animals↗

PubMed1996

A new peptide, 5-HT-moduline, isolated and purified from mammalian brain specifically interacts with 5-HT1B/1D receptors.

5-HT-Moduline (Leu-Ser-Ala-Leu) is a new endogenous peptide purified from rat brain which interacts specifically with 5-HT1B/1D receptors. The binding interaction of 5-HT-Moduline with 5-HT1B/1D receptors appeared to be a non-competitive process, since the Bmax value of [125I] cyanopindolol binding on rat brain cortical membranes was decreased without modification of the Kd. This interaction was conserved on NIH 3T3 cells expressing the 5-HT1B receptor (IC50 = 10(-11)M) suggesting that the binding site for 5-HT-Moduline is localized on the 5-HT1B receptor protein. The observed interaction may lead to functional alterations of 5-HT1B/1D receptors known to play an important role in regulating the release of 5-HT from serotonergic nerve terminals (autoreceptors) as well as the release of other neurotransmitters (heteroreceptors).

Amino Acid Sequence↗

PubMed1996

Cellular localization of 5-HT1B receptor mRNA in the rat olfactory tubercle: do GABAergic neurons express the 5-HT1B gene?

In situ hybridization with a 5-HT1B receptor probe and immunocytochemistry with gamma-aminobutyric acid (GABA) antibody performed on adjacent sections of rat brains reveal that GABAergic cell bodies, which represent 10-15% of the cellular population, do not express the 5-HT1B gene in rat olfactory tubercle. Most of the cells expressing the 5-HT1B gene were of small to medium size; large neurons expressing RNA transcripts may correspond to cholinergic neurons. It cannot be excluded that the absence of detectable 5-HT1B mRNA in GABAergic neurons was due to limited sensitivity of the in situ hybridization and immunocytochemistry procedures. Our data suggest that GABAergic neurons originating from olfactory tubercle are not directly controlled by serotonin through 5-HT1B receptors.

Animals↗