Lysergic acid diethylamide (LSD) is a partial agonist of D2 dopaminergic receptors and it potentiates dopamine-mediated prolactin secretion in lactotrophs in vitro

Giacomelli, Sabrina; Palmery, Maura; Romanelli, L.; Cheng, C. Yan; Silvestrini, Bruno

doi:10.1016/s0024-3205(98)00262-8

Cited by 45 publications

(27 citation statements)

References 16 publications

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“…(Figure 4). present data that LSD stimulated the incorporation of [ 35 S]GTP-g-S less than dopamine are consistent with the partial agonist action of LSD reported by Giacomelli et al 23 Phencyclidine also stimulates dopamine receptors by a direct or indirect action, lowering the release of prolactin 25 and causing rotation. 6,7 Although prolactin release from hemi-pituitary glands in vitro was not directly inhibited by 1 mM phencyclidine, 25 lower concentrations of phencyclidine need to be tested to determine whether phencyclidine can directly alter the release of prolactin release in vitro.…”

Section: Discussionsupporting

confidence: 93%

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Dopamine receptor contribution to the action of PCP, LSD and ketamine psychotomimetics

2005

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Although phencyclidine and ketamine are used to model a hypoglutamate theory of schizophrenia, their selectivity for NMDA receptors has been questioned. To determine the affinities of phencyclidine, ketamine, dizocilpine and LSD for the functional high-affinity state of the dopamine D2 receptor, D2 High , their dissociation constants (K i ) were obtained on [ 3 H]domperidone binding to human cloned dopamine D2 receptors. Phencyclidine had a high affinity for D2 High with a K i of 2.7 nM, in contrast to its low affinity for the NMDA receptor, with a K i of 313 nM, as labeled by [ 3 H]dizocilpine on rat striatal tissue. Ketamine also had a high affinity for D2 High with a K i of 55 nM, an affinity higher than its 3100 nM K i for the NMDA sites. Dizocilpine had a K i of 0.3 nM at D2 High , but a K d of 1.8 nM at the NMDA receptor. LSD had a K i of 2 nM at D2 High . Because the psychotomimetics had higher potency at D2 High than at the NMDA site, the psychotomimetic action of these drugs must have a major contribution from D2 agonism. Because these drugs have a combined action on both dopamine receptors and NMDA receptors, these drugs, when given in vivo, test a combined hyperdopamine and hypoglutamate theory of psychosis. Keywords: dopamine receptor; phencyclidine; domperidone; ketamine; NMDA receptors; psychotomimetics While the clinical anti-dopaminergic actions of antipsychotic drugs are compatible with the hyperdopamine hypothesis of psychosis and schizophrenia, 1,2 the psychoses caused by glutamate antagonists such as phencyclidine or ketamine suggest a hypo-glutamate component in psychosis. [3][4][5] However, phencyclidine also lowers plasma prolactin 6 and elicits rotation, 7 suggesting a direct or indirect dopaminemimetic action of phencyclidine.Although phencyclidine and ketamine are not selective for glutamate NMDA receptors, 8 the precise affinities of these drugs for dopamine D2 receptors need to be clarified in order to determine their dopaminergic and non-dopaminergic components of action. More specifically, although phencyclidine had a dissociation constant of 37 000 nM at the D2 receptor in rat striatal homogenate, 8 phencyclidine had a dissociation constant of 1.3 nM for the functional high-affinity site of the cloned D2 receptor, or the D2 High receptor. 9 This apparent discrepancy may be resolved by the recent finding that dopamine itself has a dissociation constant of 3000 nM when competing vs [ 3 H]raclopride at striatal D2 receptors, but has a dissociation constant of 1.5 nM at the D2 High receptor when the link between dopamine D1 and D2 receptors is blocked by the D1 antagonist SCH23390. 10 The link between D1 and D2 receptors arises from several sources, including the colocalization of dopamine D1 and D2 receptors in at least 50% of the medium spiny neurons in the striatum, the cooperation and mutual potentiation of D1 and D2 agonists on various behaviors, and the biochemical conversion of D2 receptors from their functional high-affinity state, D2 High , into their low-affinity state, D2 Lo...

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Section: Discussionsupporting

confidence: 93%

“…22 LSD is a known direct-acting partial agonist at dopamine D2 receptors, lowering the release of prolactin and stimulating rotation. 23,24 The Agonists N-propyl-norapomorphine-(À) 1 1 74 Apomorphine 5607100 SE for triplicate measurements. (Figure 4).…”

Section: Discussionmentioning

confidence: 99%

Dopamine receptor contribution to the action of PCP, LSD and ketamine psychotomimetics

2005

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“…Fourth, LSD bound to adrenergic and dopaminergic receptors at submicromolar concentrations, which was not the case for any of the other substances. Dopamine D 2 receptors may therefore contribute to the effects of LSD (Giacomelli et al, 1998;Marona-Lewicka et al, 2005) but are not or less involved in the action of tryptamines. Finally, all of the tryptamines inhibited the SERT in the case of DiPT at submicromolar concentrations, similar to MDMA.…”

Section: Discussionmentioning

confidence: 99%

Receptor interaction profiles of novel psychoactive tryptamines compared with classic hallucinogens

Rickli

Moning

Hoener

et al. 2016

European Neuropsychopharmacology

255

266

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“…LSD binds to dopaminergic D 2 receptors (84). LSD inhibited prolactin secretion by rat pituitary cells (85) and decreased plasma levels of prolactin in rats (86). This led to the suggestion that LSD acts as a dopamine D 2 receptor agonist in the pituitary.…”

Section: Autonomic and Endocrine Effectsmentioning

confidence: 99%

Acute Effects of Lysergic Acid Diethylamide in Healthy Subjects

Schmid¹,

Enzler²,

Gasser

et al. 2015

Biological Psychiatry

355

439

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Lysergic acid diethylamide (LSD) is a partial agonist of D2 dopaminergic receptors and it potentiates dopamine-mediated prolactin secretion in lactotrophs in vitro

Cited by 45 publications

References 16 publications

Dopamine receptor contribution to the action of PCP, LSD and ketamine psychotomimetics

Dopamine receptor contribution to the action of PCP, LSD and ketamine psychotomimetics

Receptor interaction profiles of novel psychoactive tryptamines compared with classic hallucinogens

Acute Effects of Lysergic Acid Diethylamide in Healthy Subjects

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