Role of 5-HT2A and 5-HT2C receptors in the stimulus effects of hallucinogenic drugs. II: Reassessment of LSD false positives.
David Fiorella, R A Rabin, Jerrold C Winter
Psychopharmacology October 1995 DOI: 10.1007/bf02246075 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal drug-discrimination study Peer reviewed |
|---|---|
| Population | Rats (animal subjects) |
| Interventions | (-)DOM quipazine lisuride MK-212 yohimbine pirenpirone ketanserin thiothixene |
| Dose | (-)DOM 0.56 mg/kg; quipazine 3.0 mg/kg; lisuride 0.2 mg/kg; MK-212 0.1-1.0 mg/kg; yohimbine 2-20 mg/kg; pirenpirone 0.08 mg/kg; ketanserin 2.5 mg/kg; thiothixene 0.1-1.0 mg/kg |
| Topics | LSD Serotonin |
| Key points | Quipazine and lisuride fully generalized to the (-)DOM stimulus, whereas MK-212 and yohimbine only partially generalized. The substitutions were blocked by pirenpirone and ketanserin but not by the D2 antagonist thiothixene, suggesting 5-HT2A agonist activity mediates the substitution. The authors conclude that 5-HT2A agonist activity may be required but not sufficient for hallucinogenic activity in humans, and that MK-212 and yohimbine are neither LSD nor (-)DOM false positives. |
Abstract
In the context of animal studies of hallucinogens, an LSD-false positive is defined as a drug known to be devoid of hallucinogenic activity in humans but which nonetheless fully mimics LSD in animals. Quipazine, MK-212, lisuride, and yohimbine have all been reported to be LSD false positives. The present study was designed to determine whether these compounds also substitute for the stimulus effects of the more pharmacologically selective hallucinogen (-)DOM (0.56 mg/kg, 75-min pretreatment time). The LSD and (-)DOM stimuli fully generalized to quipazine (3.0 mg/kg) and lisuride (0.2 mg/kg), but only partially generalized to MK-212 (0.1-1.0 mg/kg) and yohimbine (2-20 mg/kg). In combination tests, pirenpirone (0.08 mg/kg), a compound with both D2 and 5-HT2A affinity, blocked the substitution of quipazine and lisuride for the (-)DOM stimulus. Ketanserin (2.5 mg/kg), an antagonist with greater than 1 order of magnitude higher affinity for 5-HT2A receptors than either 5-HT2C or D2 receptors, also fully blocked the substitution of these compounds for the (-)DOM stimulus, while the selective D2 antagonist thiothixene (0.1-1.0 mg/kg) failed to block the substitution of lisuride for the (-)DOM stimulus. These results suggest that quipazine and lisuride substitute for the stimulus properties of the phenylalkglamine hallucinogen (-)DOM via agonist activity at 5-HT2A receptors. In addition, these results suggest that 5-HT2A agonist activity may be required, but is not in itself sufficient, for indolamine and phenylalkglamine compounds to elicit hallucinations in humans. Finally, it is concluded that MK-212 and yohimbine are neither LSD nor (-)DOM false positives.
Comparable studies
Other preclinical and animal studies on LSD, most cited first.
Citations in the library
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- Animal Models of Serotonergic Psychedelics ACS Chemical Neuroscience September 24, 2012
- Hallucinogen-like actions of 5-methoxy-N,N-diisopropyltryptamine in mice and rats. Pharmacology, Biochemistry, and Behavior 2006
- The serotonin 2C receptor potently modulates the head-twitch response in mice induced by a phenethylamine hallucinogen Psychopharmacology February 19, 2010
- Effect of Hallucinogens on Unconditioned Behavior Current Topics in Behavioral Neurosciences 2016
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