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Enhancing action of LSD on neuronal responsiveness to serotonin in a brain structure involved in obs

Enhancing action of LSD on neuronal responsiveness to serotonin in a brain structure involved in obs

  1. ex-junkie
    Zghoul, T. & Blier, P. (2003). Enhancing action of LSD on neuronal responsiveness to serotonin in a brain structure involved in obsessive–compulsive disorder. International Journal of Neuropsychopharmacology, 6, 13–21.doi: 10.1017/S1461145702003218

    Abstract
    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 an 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. 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 anaesthesia. In order to determine whether LSD could also exert a 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 mg/kg i.p.) for 4 d and the experiments were carried out 24 h after the last dose. LSD attenuated the firing activity of OFC neurons, and 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. It is postulated that some hallucinogens could have a beneficial action in OCD by enhancing the responsiveness to 5-HT in the OFC, and not necessarily in direct relation to hallucinosis. The latter observation may have theoretical implications for the pharmacotherapy of OCD.