Effects of serotonin agonists LSD and 25CN-NBOH on conditioned place preference and on synaptic plasticity of VTA dopamine neurons in mice
bioRxiv – December 12, 2024
Source: medRxiv/bioRxiv/arXiv
Summary
Recent findings highlight that LSD and a related compound, 25CN-NBOH, do not create strong preferences in mice, supporting the idea that psychedelics are not addictive. However, these substances did enhance synaptic plasticity in key dopamine neurons, suggesting they may influence brain reward systems in unique ways.
Abstract
The current research on psychedelic compounds such as lysergic amide diethylamide (LSD) is leaning heavily on the notion that psychedelics are not addictive. While much of the literature supports this argument, some of the common use patterns and the descriptions of the subjective effects of these compounds in humans, together with rather lacking and mixed data from non-human animal studies leave room for questions of potentially rewarding or reinforcing stimulus effects. Initiated by a surprising finding in a control study, we investigated these potential rewarding effects of LSD and a selective 5-HT2A agonist 25CN-NBOH using both unbiased and biased designs of conditioned place preference as well as ex vivo patch-clamp electrophysiology measurements of glutamatergic synaptic plasticity on midbrain ventral tegmental area (VTA) dopamine neurons in C57Bl6/J mice. Our results showed no reliable formation of place preference with either compound, agreeing with previous claims of psychedelics having at most weak reinforcing effects. However, we did observe single doses of the drugs, especially LSD, inducing synaptic plasticity in the medially located VTA dopamine neurons, implicating a role for the midbrain dopamine system in the effects of psychedelic drugs.