Complex stimulus properties of LSD: a drug discrimination study with alpha 2-adrenoceptor agonists and antagonists.
Psychopharmacology August 1995 DOI: 10.1007/bf02245809 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical behavioral pharmacology study (drug discrimination in rats) Peer reviewed |
|---|---|
| Population | Rats trained to discriminate LSD from saline |
| Interventions | Lysergic acid diethylamide (LSD) Yohimbine Idazoxan RS 26026-197 Clonidine |
| Dose | 0.08 mg/kg (186 nmol/kg) LSD training dose |
| Topics | LSD |
| Key points | Yohimbine fully substituted for the LSD discriminative cue (ED50 2.05 mg/kg), while other alpha 2-adrenergic agents did not, and clonidine shifted the LSD dose-response curve leftward. The authors argue the LSD cue can be modulated by 5-HT1A and other monoamine receptors, not solely 5-HT2 activation. |
Abstract
The influence of several alpha 2-adrenergic agents on the discriminative stimulus (DS) properties of lysergic acid diethylamide (LSD) was studied in rats trained to discriminate 0.08 mg/kg (186 nmol/kg) of LSD from saline in a two-lever operant paradigm. Only yohimbine fully mimicked LSD with an ED50 of 2.05 mg/kg (5.24 mumol/kg). Yohimbine's 5-HT1A agonist properties may be responsible for this substitution. Other alpha 2-adrenoceptor antagonists, idazoxan with an agonist/antagonist profile at 5-HT1A receptors and RS 26026-197, a highly selective alpha 2-adrenoceptor antagonist, failed to produce substitution. Clonidine, an alpha 2-adrenoceptor agonist, did not substitute for LSD but the response rate was dose-dependently reduced. None of the alpha 2-adrenergic agents used for pretreatment before LSD inhibited the response to the LSD training dose. Coadministration of clonidine with LSD produced a leftward shift of the dose-response relationship of LSD without a significant change in the slope of the dose-response line. Simultaneous administration of alpha 2-adrenergic agents with LSD shifted the dose-response curve to the left only when the adrenergic agent also possessed at least moderate affinity for the 5-HT1A receptor. In addition, radioligand competition experiments were performed that showed LSD to have relatively high affinity (Ki = 37 nM) for [3H]clonidine-labeled sites in rat cortex with lower affinity for [3H]yohimbine labeled sites. While previous studies have suggested that the nature of the LSD cue may be essentially expressed by 5-HT2 receptor activation, the present data show that this cue can be modulated by effects of LSD at 5-HT1A and at other monoamine neurotransmitter receptors.
Comparable studies
Other preclinical and animal studies on LSD, most cited first.
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Cites 12
- Evidence for 5-HT2 involvement in the mechanism of action of hallucinogenic agents. Life Sciences December 17, 1984
- Do functional relationships exist between 5-HT1A and 5-HT2 receptors? Pharmacology, Biochemistry, and Behavior August 1, 1990
- Citalopram antagonizes the stimulation by lysergic acid diethylamide of presynaptic inhibitory serotonin autoreceptors in the rat hypothalamus. Journal of Pharmacology and Experimental Therapeutics July 1, 1982
- Neuropharmacological reassessment of the discriminative stimulus properties ofd-lysergic acid diethylamide (LSD) Psychopharmacology 1987
- Characterization of the Discriminative Stimulus Properties Induced by 5‐HT1and 5‐HT2Agonists in Rats Pharmacology & Toxicology February 1, 1989
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