The novel antidepressant drug tianeptine had an antidepressant-like effect on a rat model of depression based on the deficit in open field activity observed on the day after 2 h immobilization. Thus, tianeptine (10 mg/kg ip) given 2 h after the end of the immobilization period led to the deficit being opposed. Similar results were obtained using rats previously given 10 mg/kg of the drug per day for 13 days and a final dose 2 h after the end of immobilization. Other workers have found that tianeptine attenuates stress-induced activation of the hypothalamo-pituitary-adrenal axis. Possible relationships between these findings are discussed together with the paradoxical co-existence of the antidepressant properties of tianeptine with its ability to decrease the availability of 5-HT to receptors.

Research investigating the neurobiological underpinnings of anxiety disorder have mainly been focused on dysfunction of the GABA, noradrenergic and serotonergic (5-HT) neuronal systems. Just recently, in both animal and human studies, evidence has been found for a possible role of the cholecystokinin (CCK) neuronal system in the pathogenesis of anxiety disorder.

Behaviorally, animal studies revealed anxiogenic-like properties for the ‘central’ CCKB receptor agonists, while CCKB receptor antagonists displayed intrinsic anxiolytic properties. Similarly, in man, CCKB receptor agonists, like pentagastrin and CCK4, were found to be able to elicited panic attacks in both panic disorder (PD) patients and healthy volunteers. These effects appear due to stimulation of the CCKB receptor. In addition, clinically effective panicolytic agents reduce the sensitivity to CCK4 in PD patients. Taken together, these findings may suggest a role for CCK in the neurobiology of PD. On the other hand, there is circumstantial evidence for involvement of several other neuronal systems, such as the serotonergic, noradrenergic and GABA-ergic system, in the regulation of anxiety. Interestingly, evidence has been found for an interaction between CCK and 5-HT and that this interaction plays a role in the mediation of anxiety.

This presentation will critically discuss the evidence for the role of the CCKB receptor in anxiety and in addition, will focus on the putative evidence that the role of CCK in anxiety is mediated by its interaction with the serotonergic neuronal system.

The metabolism of 5-hydroxytryptamine (5-HT), octopamine (OA) and dopamine (DA) by adult male Ascaridia galli was investigated by incubating worms cut into 5 mm lengths with radio-isotope labelled amine. [14C]5-hydroxytryptamine and [14C]octopamine were taken up by the tissues and were metabolized to apolar products that co-chromatographed using both high-performance liquid chromatography and thin-layer chromatography with N-acetyl 5-hydroxytryptamine (NA5-HT) and N-acetyloctopamine (NAOA), respectively. N-acetylation was by far the most important reaction detected under these experimental conditions. A brief incubation of cut worms with [3H]dopamine resulted in the formation of a radio-isotope labelled metabolite that co-chromatographed with N-acetyldopamine (NADA) on reversed-phase high-performance liquid chromatography. The N-acetyltransferase activity towards 5-hydroxytryptamine and octopamine was detected in crude homogenates of male worms only when the co-substrate, acetyl CoA, was added to the reaction mixture. This enzyme activity appeared to be mainly localized in a 40 000 g supernatant fraction. The failure of previous studies to detect N-acetylation of biogenic amines in tissue homogenates of nematodes may have been due to the low levels of acetyl CoA present in these enzyme preparations.

The pharyngeal component of the enteric nervous system of the parasitic nematode, Ascaris suum exhibits immunoreactivity for serotonin (5-hydroxytryptamine or 5-HT) and for FMRFamide-like peptides. This paper describes the application of an in vitro pharmacological approach to investigate the functional role of 5-HT and FMRFamide-like peptides. The pharyngeal pumping behaviour of Ascaris suum was monitored using a modified pressure transducer system which measures pharyngeal pressure changes and therefore pumping. The pharynx did not contract spontaneously; however, 5-HT (10-1000 μM) stimulated pumping at a frequency of 0·5 Hz. FMRFamide had no apparent effect on pharyngeal pumping. The native nematode FMRFamide-related peptide (FaRP), KSAYMRFamide inhibited the pumping elicited by 5-HT. The duration of inhibition was dose-dependent (0·1-1000 nM) with a threshold of 0·1 nM. In 4 preparations, the inhibition of the pharyngeal muscle was preceded by an initial excitation and increase in the amplitude of pharyngeal pressure changes. The pharynx is involved in various nematode processes, including feeding, regulation of hydrostatic pressure and excretion. The role of 5-HT and KSAYMRFamide in the pharyngeal function of nematodes is discussed.

The major muscle systems of the metacercaria of the strigeid trematode, Apatemon cobitidis proterorhini have been examined using phalloidin as a site-specific probe for filamentous actin. Regional differences were evident in the organization of the body wall musculature of the forebody and hindbody, the former comprising outer circular, intermediate longitudinal and inner diagonal fibres, the latter having the inner diagonal fibres replaced with an extra layer of more widely spaced circular muscle. Three orientations of muscle fibres (equatorial, meridional, radial) were discernible in the oral sucker, acetabulum and paired lappets. Large longitudinal extensor and flexor muscles project into the hindbody where they connect to the body wall or end blindly. Innervation to the muscle systems of Apatemon was examined by immunocytochemistry, using antibodies to known myoactive substances: the flatworm FMRFamide-related neuropeptide (FaRP), GYIRFamide, and the biogenic amine, 5-hydroxytryptamine (5-HT). Strong immunostaining for both peptidergic and serotoninergic components was found in the central nervous system and confocal microscopic mapping of the distribution of these neuroactive substances revealed they occupied separate neuronal pathways. In the peripheral nervous system, GYIRFamide-immunoreactivity was extensive and, in particular, associated with the innervation of all attachment structures; serotoninergic fibres, on the other hand, were localized to the oral sucker and pharynx and to regions along the anterior margins of the forebody.

La neurotransmission de sérotonine (5-HT) est régulée, via un rêtro-contrôle négatif, par des réceptcurs situés an niveau du raphé nucleus et des terminaisons neuronales. Ces autorécepteurs sérotoninergiques ont été étudiés aux niveaux comportemental, électrophysiologique et biochimique. Les réponses comportementales et électropliysiologiques sont atténuées par l'administration chronique des antidépresseurs. De plus, in vitro, les inhibiteurs de capture de 5-HT atténuent l'aulorégulation de la libération de [3H]5-HT. La présente étude concerne l'effet, sur cette libération induite par stimulation électrique de l'hypothalamus; de rat et sa modulation, de l'administration chronique de 2 antidépresseurs, le citalopram, inhibiteur spécifique de la capture de 5-HT, et le milnacipran (anciennement midalcipran, F 2207), qui bloque la capture de 5-HT et de noradrénaline avec la même puissance. Le eitalopram était administré à 50 et à 10 mg/kg/j pendant 21 jours et 24 h après, les rats étaient décapités, des coupes d'hypoihalamus incubées avec la [3H]5-HT, superfusées avec une solution de Krebs et stimulées électriquement. La quantité de [3H]5-HT libélée par stimulation électrique étail augmented et l'effet inhibiteur de l'agoniste, LSD, diminué chez les rats traités. Ces effets étaient présents aux 2 doses mais plus marqués à la forte dose. Donc un traitement chronique avec le citalopram provoque une «down-regulation» de l'autorécep-teur sérotonergique, permettant ainsi une augmentation de la neurotransmission de 5-HT. Cet effet peut expliquer, an moins en partie, l’action antidépressive de ce produit et it esl possible qu'il représente un mécanisme fondamental à beaucoup d'antidépresseurs qui inhibent la capture de 5-HT. Cependant, après 21 jours de traitement avec le milnacipran, à 50 mg/kg/j, aucun des paramétres étudiés n'était modifié. Cela suggère que l’hypothèse de la «down-regulation» de l’autorècepteur n'est pas l'hypothèse universelle qui explique l’action de tous les antidépresseurs agissant sur la capture de 5-HT.