Rationale. Potent serotonin (5-HT) reuptake inhibitors are the only drugs that consistently exert a therapeutic action in obsessive compulsive disorder (OCD). Given that some hallucinogens were reported to exert a persistent anti OCD effect outlasting their psychotomimetic action, possible modifications of neuronal responsiveness to 5-HT by LSD were examined in two rat brain structures: one associated with OCD, the orbitofrontal cortex (OFC), and another linked to depression, the hippocampus. Methods . The effects of concurrent microiontophoretic application of LSD and 5-HT were examined on neuronal firing rate in the rat OFC and hippocampus under chloral hydrate anesthesia. In order to determine whether LSD could also exert any modification of 5-HT neuronal responsiveness upon systemic administration, after a delay when hallucinosis is presumably no longer present, it was given once daily (100 mug/kg, i.p.) for four days and the experiments were carried out 24 hours after the last dose. Results. LSD attenuated the firing activity of OFC neurons, but enhanced the inhibitory effect of 5-HT when concomitantly ejected on the same neurons. In the hippocampus, LSD also decreased firing rate by itself but decreased the inhibitory action of 5-HT. The inhibitory action of 5-HT was significantly greater in the OFC, but smaller in the hippocampus, when examined after subacute systemic administration of LSD. Conclusions. It is postulated that some hallucinogens could have a beneficial action in OCD by enhancing 5-HT receptor responsiveness in the OFC, and not necessarily in direct relation to hallucinosis. The latter observation may have theoretical implications for the pharmacotherapy of OCD.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.29490 |
| Date | January 2001 |
| Creators | Zghoul, Tarek |
| Contributors | Blier, P. (advisor) |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Master of Science (Division of Neuroscience.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001940942, proquestno: MQ85840, Theses scanned by UMI/ProQuest. |
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