Daily LSD administration selectively decreases serotonin2 receptor binding in rat brain

Area of Science:

• Neuropharmacology
• Receptor Binding Assays
• Psychopharmacology

Background:

• Serotonin receptors, including 5-HT1 and 5-HT2 subtypes, play crucial roles in regulating mood, cognition, and behavior.
• Lysergic acid diethylamide (LSD) is a potent psychoactive substance known to interact with various serotonin receptors.
• Understanding the long-term effects of LSD on serotonin receptor binding is essential for comprehending its neurobiological impact.

Purpose of the Study:

• To investigate the impact of repeated lysergic acid diethylamide (LSD) administration on serotonin 5-HT1 and 5-HT2 receptor binding in rat brain membranes.
• To determine if chronic LSD exposure selectively alters specific serotonin receptor subtypes.

Main Methods:

• Rats received ten daily intraperitoneal injections of either saline or d-lysergic acid diethylamide (LSD) at a dose of 260 micrograms/kg.
• Brain membranes were prepared 24 hours after the final injection.
• Radioligand binding assays were performed using [3H]LSD with specific concentrations of serotonin (5-HT) and cinanserin to quantify 5-HT1 and 5-HT2 receptor binding, respectively.

Main Results:

• Lysergic acid diethylamide (LSD) administration resulted in a significant decrease in serotonin 5-HT2 receptor binding.
• This reduction in 5-HT2 binding was observed across multiple brain regions, including the cortex, striatum, hippocampus, and diencephalon/midbrain.
• No significant alterations were found in serotonin 5-HT1 receptor binding or total specific binding following LSD treatment.

Conclusions:

• Repeated exposure to lysergic acid diethylamide (LSD) selectively downregulates serotonin 5-HT2 receptors in various brain areas.
• The observed decrease in 5-HT2 receptor binding may contribute to the complex neurochemical and behavioral effects of LSD.
• Serotonin 5-HT1 receptors appear to be unaffected by this chronic LSD treatment regimen.