PubMed Health⌕ Search
Home/Archive/PubMed

PubMed · 3667104

Serotonin and kindling development.

M Lerner-Natoli
View original source ↗Export metadata ↓

Abstract

The inhibitory effect of serotonin on the kindling model of epilepsy was investigated in the adult rat. Specific neurotoxins such as 5-6 or 5-7 dihydroxytryptamine were used to destroy serotoninergic neurons before kindling sessions, and an immunocytochemical control revealed, at the end of the experiments, the location and the extent of the lesions. The destruction of serotoninergic terminals in the epileptic focus (olfactory bulb or amygdala) facilitated the initial development of kindling obtained by stimulations of these structures. Lesions of pontis, centralis and dorsalis nuclei of the raphe enhanced the rate of olfactory bulb kindling. Finally, we transplanted foetal raphe cells into the olfactory bulb of adult rats before olfactory bulb kindling. The presence of viable grafts, controlled by immunocytochemistry, was associated with an increase of afterdischarge threshold in the olfactory bulb. All these results confirm the inhibitory function of serotonin on kindling development and demonstrate that serotoninergic neurons exert an important control both on local excitability and on the progressive establishment of kindling phenomena.

Explore related subjects

5,6-Dihydroxytryptamine5,7-DihydroxytryptamineAmygdalaAnimalsFemaleKindling, NeurologicMaleNeurotoxinsOlfactory BulbRaphe NucleiRatsRats, Inbred StrainsSerotoninJournal Article

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

M Lerner-Natoli. 1987. Serotonin and kindling development.. https://doi.org/10.3109/00207458709058789

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2006

Comparative studies of the effects of chlorpromazine and 5,6-dihydroxytryptamine on locomotion, defensive reactions in the snail Helix lucorum, and command neuron excitability in long-term sensitization.

The actions of the neuroleptic chlorpromazine (CPZ) and the neurotoxin 5,6-dihydroxytryptamine (5,6-DHT) on defensive reactions, locomotion, formation of long-term sensitization, and the electrical characteristics of command neurons in the common snail were compared. Prolonged (chronic) treatment with CPZ led to a significant increase in the pneumostoma closure time, as well as changes in motor behavior, with a decrease in the rate of locomotion. Administration of 5,6-DHT in small daily doses for one week was accompanied by gradual decreases in the rate of locomotion of the snails, which persisted for one week. A similar effect was seen after administration of the same total dose of neurotoxin, 30 mg/kg, as a single injection. Administration of CPZ prevented the formation of long-term sensitization, as did treatment with 5,6-DHT. The procedures of treatment with CPZ, long-term sensitization, long-term sensitization followed by CPZ, and acquisition of long-term sensitization on the background of treatment with CPZ gave a locomotion speed which was directly proportional to the length of the sole. No such relationship was seen during the acquisition of long-term sensitization on the background of treatment with 5,6-DHT. Electrophysiological studies showed that chronic CPZ led to a depolarization shift in the membrane potential and a decreased action potential generation threshold in command neurons, which also occurred on treatment with 5,6-DHT. It is concluded that the actions of the neuroleptic CPZ on defensive behavior and locomotion in the common snail, as well as on the electrical characteristics of identified neurons, were similar to the toxic actions of serotonin.

5,6-Dihydroxytryptamine↗
PubMed2005

Involvement of supraspinal imidazoline receptors and descending monoaminergic pathways in tizanidine-induced inhibition of rat spinal reflexes.

The neuronal pathways involved in the muscle relaxant effect of tizanidine were examined by measurement of spinal reflexes in rats. Tizanidine (i.v. and intra-4th ventricular injection) decreased the mono- and disynaptic (the fastest polysynaptic) reflexes (MSR and DSR, respectively) in non-spinalized rats. Depletion of central noradrenaline by 6-hydroxydopamine abolished the depressant effect of tizanidine on the MSR almost completely and attenuated the effect on the DSR. Co-depletion of serotonin by 5,6-dihydroxytryptamine and noradrenaline resulted in more prominent attenuation of tizanidine-induced inhibition of the DSR. Supraspinal receptors were then studied using yohimbine- and some imidazoline-receptor ligands containing an imidazoline moiety. Idazoxan (I1, I2, I3, and alpha2), efaroxan (I1, I3, and alpha2), and RX821002 (I3 and alpha2), but not yohimbine, an alpha2-adrenergic receptor antagonist with no affinity for I receptors, antagonized the inhibitory effects of tizanidine. Thus, supraspinal I receptors (most likely I3) and descending monoaminergic influences are necessary for tizanidine-induced inhibition of spinal segmental reflexes.

5,6-Dihydroxytryptamine↗
PubMed2005

Imidazoline receptors associated with noradrenergic terminals in the rostral ventrolateral medulla mediate the hypotensive responses of moxonidine but not clonidine.

We determined whether the cardiovascular actions of central anti-hypertensive agents clonidine and moxonidine are dependent on noradrenergic or serotonergic innervation of the rostral ventrolateral medulla (RVLM) in conscious rabbits. 6-Hydroxydopamine (6-OHDA) or 5,6-dihydroxytriptamine (5,6-DHT) was injected into the RVLM to deplete noradrenergic and serotonergic terminals respectively. One, 2 and 4 weeks later, responses to fourth ventricular (4V) clonidine (0.65 microg/kg) and moxonidine (0.44 microg/kg) were examined. Destruction of noradrenergic pathways in the RVLM by 6-OHDA reduced the hypotensive response to 4V moxonidine to 62%, 47% and 60% of that observed in vehicle treated rabbits at weeks 1, 2 and 4 respectively. The moxonidine induced bradycardia was similarly attenuated (to 46% of vehicle). Conversely, 6-OHDA had no effect on the hypotensive or bradycardic effects of 4V clonidine. Efaroxan (I(1)-imidazoline receptor/alpha(2)-adrenoceptor antagonist; 3.5, 11, 35 microg/kg) and 2-methoxyidazoxan (alpha(2)-adrenoceptor antagonist; 0.3, 0.9, 3 microg/kg) equally reversed the hypotension to 4V clonidine, suggesting a mainly alpha(2)-adrenoceptor mechanism. Efaroxan preferentially reversed responses to moxonidine in both vehicle and 5,6-DHT groups and in the 1st week after 6-OHDA, suggesting a mechanism involving mainly I(1)-imidazoline receptors. This selectivity was subsequently lost in the 2nd and 4th weeks when the remaining hypotension was mainly mediated by alpha(2)-adrenoceptors. Depletion of serotonergic terminals did not alter the responses to either agonist nor did it change the relative effectiveness of the antagonists. Western blots of RVLM tissues probed with imidazoline and alpha(2)-adrenoceptor antisera showed a pattern of bands close to that reported in other species. The main effect of 6-OHDA was an 18% lower level of the 42 kDa imidazoline protein (P<0.05). We conclude that the hypotensive and bradycardic actions of moxonidine but not clonidine are mediated through imidazoline receptors and are dependent on intact noradrenergic pathways within the RVLM. Furthermore, the noradrenergic innervation may be associated with a 42 kDa imidazoline receptor protein.

5,6-Dihydroxytryptamine↗