Enhancing action of LSD on neuronal responsiveness to serotonin in a brain structure involved in obsessive–compulsive disorder
The International Journal of Neuropsychopharmacology – March 01, 2003
Source: OpenAlex
Summary
LSD may offer therapeutic benefits for obsessive-compulsive disorder (OCD) by enhancing serotonin responsiveness in the orbitofrontal cortex (OFC). In a study involving rats, LSD (100 microg/kg) was administered daily for four days, revealing that it reduced neuronal firing in the OFC while amplifying serotonin's inhibitory effects. Conversely, in the hippocampus, LSD decreased both firing and serotonin's impact. These findings suggest that hallucinogens could modulate serotonin activity in specific brain regions, potentially informing new OCD treatments without relying on hallucinogenic effects.
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 microg/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.