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von Hungen K, Roberts S, Hill DF.
“LSD as an agonist and antagonist at central dopamine receptors.”.
Nature. 1974;252(5484):588-589.
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Abstract
Agonistic and antagonistic activities of D-LSD (D-lysergic acid diethylamide) at cerebral dopamine receptors were studied. Method The effects of D-LSD, L-LSD and 2-bromo-D-lysergic acid diethylamide (BOL) on the activation of adenyl cyclase induced by L-noradrenaline plus dopamine and those of D-LSD, chlorpromazine, haloperidol, i-methyl-D-lysergic acid diethylamide (MLD), BOL, propranolol or cyproheptadine on dopamine- and D-LSD-induced activation of adenyl cyclase were determined in particulate fractions from cerebral cortex or corpus striatum of male rats (-6 weeks, 225 g). Results The conversion of 14G-ATP to cyclic AMP (i.e. the adenyl cyclase activity) was completely blocked by 10 M D-LSD, and 10 M dopamine plus 10 M noradrenaline had additive effects on adenyl cyclase activity. The response to dopamine and noradrenaline was also inhibited by 10 M BOL. The stimulation of the enzyme activity by either dopamine or noradrenaline was also inhibited by L-LSD in particulate hippocampal preparations from rat--brain. Although hypothalamic, brain stem and cerebellar cell-;free fractions did not Show any activation of adenyl cyclase activity in response to D-LSD, this effect could be elicited in cell-free fractions obtained from striatal tissue with very low D-LSD concentrations (0.1 M). 10 M D-LSD was about half as effective in enhancing enzyme activity in particulate preparations from corpus striatum of adult rats as equimolar doses of dopamine. 10 M of D-LSD, however, completely abolished the effects of 10 M dopamine. 10 M of chlorpromazine or haloperidol, 100 M of BOL or MAD or cyproheptadine almost completely abolished the effects of equimolar doses of either D-LSD or dopamine. D-LSD or dopamine-induced enhancement of adenyl cyclase in striatal tissue was not inhibited by propranolol The enzyme activity in striatal tissue was not stimulated by any of the blocking agents themselves, except D-LSD.
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