LSD as an agonist of dopamine receptors in the striatum

Pieri, L.; Pieri, Margherita; Haefely, W.

doi:10.1038/252586a0

Cited by 126 publications

(35 citation statements)

References 15 publications

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“…Although LSD was originally described as an agent that blocks cerebral 5-hydroxytryptamine receptors (Boakes, Bradley, Briggs & Dray, 1970) and inhibits the release of this transmitter from central neurones (Chase, Breese & Kopin, 1967), later evidence suggests that it may stimulate 5-hydroxytryptamine receptors (Anden, Corrodi, Fuxe & Hokfelt, 1968;Aghajanian, 1972). Further, it has now been suggested that LSD is also a potent dopamine receptor agonist, for it causes strong contraversive turning in rats with unilateral lesions of the medial forebrain bundle (Pieri, Pieri & Haefely, 1974). However, no such effect was found in the present study, where only nigro-striatal terminals were damaged by the unilateral 6-hydroxydopamine lesion (Pycock & Anlezark, 1975 Costall & Naylor (1974) have shown that a unilateral electrolytic lesion in the 5-hydroxytryptaminergic raphe nuclear system will result in a rat that circles in response to drugs.…”

Section: Discussionmentioning

confidence: 99%

Effects of Drugs Acting on Cerebral 5‐hydroxytryptamine Mechanisms on Dopamine‐dependent Turning Behaviour in Mice

Milson¹,

Pycock²

1976

British J Pharmacology

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I The effects of drugs acting on cerebral 5-hydroxytryptaminergic mechanisms on drug-induced turning behaviour in mice with unilateral destruction of nigro-striatal dopaminergic nerve terminals have been studied. 2 Administration of L-tryptophan (400 mg/kg) or 5-hydroxytryptophan (200 mg/kg) increased brain 5-hydroxytryptamine and decreased the turning induced by both apomorphine (2 mg/kg) and amphetamine (5 mg/kg). 3 Parachlorophenylalanine (3 x 500 mg/kg) decreased brain 5-hydroxytryptamine and increased both apomorphine and amphetamine-induced circling behaviour. 4 Varying the protein content of dietary intake significantly altered brain 5-hydroxytryptamine and tryptophan levels, spontaneous locomotor activity and amphetamine-induced circling behaviour in these mice. 5Systemic administration of methysergide (0.5-4 mg/kg), lysergic acid diethylamide (0.025-0.2 mg/kg), cyproheptadine (2.5-20 mg/kg) or clomipramine (0.6-20 mg/kg) produced no consistent effect on drug-induced turning behaviour. 6 The results suggest that circling behaviour due to striatal dopamine receptor stimulation is depressed by an elevation of brain 5-hydroxytryptamine and enhanced by a reduction in brain 5-hydroxytryptamine. 7 The possible physiological relationship between dopamine and 5-hydroxytryptamine neurones in the basal ganglia is discussed.

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Section: Discussionmentioning

confidence: 99%

Effects of Drugs Acting on Cerebral 5‐hydroxytryptamine Mechanisms on Dopamine‐dependent Turning Behaviour in Mice

Milson¹,

Pycock²

1976

British J Pharmacology

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“…In animal models this has been demonstrated with regard to particular behavioral effects such as the head-twitch response, as well as drug discrimination models (Fantegrossi et al, 2004, Carbonaro et al, 2014). However, differential actions at other serotonergic, dopaminergic, and downstream glutamatergic targets are known to modulate the effects of distinct psychedelics (Moreno et al, 2011; Nichols, 2016; Pieri et al, 1974; Ray, 2010; Vollenweider et al, 1999; Vollenweider & Kometer, 2010). Animal models have not found consistent self-administration of LSD in suggesting a low addictive potential for this drug class (Fantegrossi et al 2008; Hoffmeister & Wuttke, 1975; Poling & Bryceland, 1979; Schuster & Thompson, 1969).…”

Section: Introductionmentioning

confidence: 99%

Clinical applications of hallucinogens: A review.

Garcia-Romeu

Kersgaard

Addy³

2016

Experimental and Clinical Psychopharmacology

144

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Hallucinogens fall into several different classes, as broadly defined by pharmacological mechanism of action, and chemical structure. These include psychedelics, entactogens, dissociatives, and other atypical hallucinogens. Although these classes do not share a common primary mechanism of action, they do exhibit important similarities in their ability to occasion temporary but profound alterations of consciousness, involving acute changes in somatic, perceptual, cognitive, and affective processes. Such effects likely contribute to their recreational use. However, a growing body of evidence indicates that these drugs may have therapeutic applications beyond their potential for abuse. This review will present data on several classes of hallucinogens with a particular focus on psychedelics, entactogens, and dissociatives, for which clinical utility has been most extensively documented. Information on each class is presented in turn, tracing relevant historical insights, highlighting similarities and differences between the classes from the molecular to the behavioral level, and presenting the most up-to-date information on clinically oriented research with these substances, with important ramifications for their potential therapeutic value.

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“…LSD is considered to be a central nervous system 5-HT agonist (And~n et al, 1968;Aghajanian et aL, 1972), and has been found to inhibit the estrogen + progesterone-activated lordotic behavior dosedependently (> 0.05 mg/kg) Meyerson, 1976, 1977;Sietnieks and Meyerson, 1980). Some authors have claimed that LSD also influcences dopaminergic receptors ( Grabowska et aL, 1974;Pieri et al, 1974;Da Prada et aL, 1975). However, Eliasson and Meyerson (1976) demonstrated that the predominant action of LSD on the female copulatory response is not mediated by increased dopamine activity, as the selective dopamine antagonist pimozide did not prevent the LSD-induced decrease in L.R.…”

Section: Discussionmentioning

confidence: 95%

Involvement of 5-HT2 receptors in the LSD- and L-5-HTP-induced suppression of lordotic behavior in the female rat

Sietnieks

1985

J. Neural Transmission

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Copulatory behavior in the ovariectomized rat, the lordotic response (L.R.), was induced by estrogen followed by progesterone. L.R. is inhibited by lysergic acid diethylamide (LSD) (greater than or equal to 0.05 mg/kg) and by Levo-5-hydroxytryptophan (L-5-HTP) (greater than or equal to 2.5 mg/kg). The effects of the putative 5-HT antagonists lisuride, metergoline, methysergide, mianserin, cinanserin, cyproheptadine, pirenperone and altanserin on the LSD-induced inhibition of L.R. were tested. Lisuride, metergoline, methysergide and mianserin were found to have no LSD-blocking effect. In contrast, cinanserin, cyproheptadine and pirenperone acted antagonistically to LSD, within a critical dose range. The selective 5-hydroxytryptamine2 (5-HT2) receptor antagonist altanserin effectively prevented the LSD-induced inhibition of L.R., and the doses required (0.05-0.20 mg/kg) indicated a comparatively high antagonistic potency. In addition altanserin (0.2 mg/kg) effectively prevented the lordosis inhibitory effect induced by L-5-HTP (2.5 mg/kg), after pretreatment with pargyline and RO4-4602. It is suggested that the suppression of copulatory behavior caused by LSD and L-5-HTP is mediated by 5-HT2 receptors.

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LSD as an agonist of dopamine receptors in the striatum

Cited by 126 publications

References 15 publications

Effects of Drugs Acting on Cerebral 5‐hydroxytryptamine Mechanisms on Dopamine‐dependent Turning Behaviour in Mice

Effects of Drugs Acting on Cerebral 5‐hydroxytryptamine Mechanisms on Dopamine‐dependent Turning Behaviour in Mice

Clinical applications of hallucinogens: A review.

Involvement of 5-HT2 receptors in the LSD- and L-5-HTP-induced suppression of lordotic behavior in the female rat

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