Effect of tianeptine on the central cholinergic system: involvement of serotonin.
The effect of tianeptine on in vivo acetylcholine (ACh) release from brain hemispheric regions of freely moving rats was investigated using the microdialysis technique coupled with a sensitive radioenzymatic method. Tianeptine, at the dose of 30 mg/kg i.p., reduced ACh release from dorsal hippocampi by 40% in 40 min, and induced a 30% decrease of ACh output from frontal cortices while at the doses of 10 and 20 mg/kg it had no effect. In striata the drug did not significantly affect ACh release although it showed a tendency to increase it. The ACh content in the three areas considered was not affected by tianeptine at above doses. The drug did not alter choline-o-acetyltransferase and acetylcholinesterase activities suggesting that it did not influence the cholinergic system through direct action on the ACh metabolism; furthermore, it did not influence the sodium-dependent high-affinity uptake of choline in striatum, cortex and hippocampus. Impairment of serotonergic (5-HT) neurotransmission by chemical lesion of the median raphe nucleus or by metergoline, a blocker of 5-HT receptors, antagonized the cholinergic effect of tianeptine. The involvement of the serotonergic system is specific because lesions of the noradrenergic dorsal bundle failed to prevent the inhibitory action of tianeptine. The present data suggest that 5-HT may mediate the effect of tianeptine on the cholinergic system in dorsal hippocampi.
Bertorelli
R
R
Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
Amoroso
D
D
Girotti
P
P
Consolo
S
S
D000109:Acetylcholine / Q000378:metabolism; D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D001927:Brain Diseases / Q000503:physiopathology; D002794:Choline / Q000378:metabolism; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D002799:Cholinergic Fibers / Q000187:drug effects* / Q000378:metabolism; D002997:Clomipramine / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D011903:Raphe Nuclei / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000494:pharmacology*; D012964:Sodium / Q000502:physiology; D013841:Thiazepines / Q000494:pharmacology*
D000929:Antidepressive Agents, Tricyclic; D013841:Thiazepines; C050504:tianeptine; D012701:Serotonin; D012964:Sodium; D002795:Choline O-Acetyltransferase; D000110:Acetylcholinesterase; D002794:Choline; D000109:Acetylcholine; D002997:Clomipramine