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LSD as an agonist at mesolimbic dopamine receptors
Psychopharmacologia
|December 31, 1975
Summary
Lysergic acid diethylamide (LSD) stimulates locomotor activity in rats with dopamine-depleted nucleus accumbens, suggesting LSD acts as a dopamine agonist. This effect was blocked by a dopamine antagonist, confirming the dopamine receptor interaction.
Area of Science:
- Neuroscience
- Pharmacology
Background:
- The nucleus accumbens is a key component of the mesolimbic dopamine pathway involved in reward and motivation.
- Dopamine depletion in the nucleus accumbens, induced by 6-hydroxydopamine (6OHDA), models aspects of Parkinson's disease and addiction.
Purpose of the Study:
- To investigate the effects of lysergic acid diethylamide (LSD) on locomotor activity in a rat model of dopamine depletion.
- To determine if LSD's effects are mediated by dopamine receptors.
Main Methods:
- Rats received bilateral 6-hydroxydopamine (6OHDA) injections into the nucleus accumbens.
- Locomotor activity was measured after administration of apomorphine, LSD, or (+)-bromo-lysergic acid diethylamide.
- The effect of the dopamine antagonist pimozide on LSD-induced activity was assessed.
Main Results:
- Apomorphine enhanced locomotor activity in 6OHDA-treated rats compared to controls.
- LSD significantly stimulated locomotor activity in 6OHDA-treated rats at a dose ineffective in controls.
- (+)-Bromo-lysergic acid diethylamide did not affect locomotor activity in 6OHDA-treated rats.
- Pimozide pretreatment blocked LSD-induced locomotor stimulation.
Conclusions:
- LSD acts as an agonist at mesolimbic dopamine receptors.
- The findings suggest a role for dopamine receptor agonism in LSD's psychopharmacological effects.
- This study provides evidence for LSD's interaction with the mesolimbic dopamine system.