Serotonin2 agonist administration down-regulates rat brain serotonin2 receptors

Area of Science:

• Neuroscience
• Pharmacology
• Receptor Binding Assays

Background:

• D-lysergic acid diethylamide (LSD) administration decreases serotonin 5-HT2 receptor binding.
• 4-substituted phenylisopropylamine derivatives, DOI and DOB, are identified as selective 5-HT2 agonists.
• These agonists share behavioral and neurophysiological effects with LSD, suggesting 5-HT2 receptor mediation.

Purpose of the Study:

• To investigate if DOI and DOB affect 5-HT2 receptor binding similarly to LSD after systemic administration.
• To determine the time course of 5-HT2 receptor binding changes following administration of LSD and 5-HT2 agonists.
• To confirm the down-regulatory capacity of 5-HT2 agonists on 5-HT2 receptors.

Main Methods:

• Rats were administered daily doses of LSD, DOI, or DOB.
• 5-HT2 receptor binding was evaluated using [3H]ketanserin.
• Binding assays were conducted at various time points (4 hours, 24 hours) after single high doses and after 7 days of daily administration.

Main Results:

• Daily administration of DOI (1.0 mg/kg) or DOB (0.5 mg/kg) for 7 days decreased 5-HT2 binding, mirroring LSD effects.
• A single high dose of LSD (650 µg/kg) or DOI (7.0 mg/kg) decreased 5-HT2 binding 24 hours post-administration.
• Significant decreases in 5-HT2 binding were observed as early as 4 hours after a single high dose of LSD or DOI.

Conclusions:

• 5-HT2 receptor agonists, including DOI and DOB, are capable of down-regulating 5-HT2 receptors.
• LSD acts in parallel with selective 5-HT2 agonists regarding 5-HT2 receptor down-regulation.
• 5-HT2 receptor binding can be significantly modified within hours of drug administration.