Cross-tolerance studies of serotonin receptors involved in behavioral effects of LSD in rats.
K M Krebs, Mark A. Geyer
Psychopharmacology January 1994 DOI: 10.1007/bf02245219 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Controlled animal experiment (cross-tolerance regimen) Peer reviewed |
|---|---|
| Population | Rats tested in a behavioral pattern monitor |
| Interventions | LSD 8-hydroxy-2(di-n-propylamino)-tetralin (8-OH-DPAT) 1-(2 5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) saline |
| Dose | 8-OH-DPAT 0.5 mg/kg SC; DOI 1.0 mg/kg SC; LSD 60 micrograms/kg SC |
| Duration | Pretreatment every 12 h for 5 or 8 days; testing 36 hours later |
| Topics | LSD Serotonin |
| Key findings | Chronic pretreatment with 8-OH-DPAT or DOI produced cross-tolerance to LSD's effects on locomotor activity and investigatory behavior in rats. The authors argue this supports the hypothesis that LSD's effects in this model reflect a combination of 5-HT1A and 5-HT2 receptor actions, and that the two receptor systems interact. |
Abstract
Like hallucinogenic 5-HT2 agonists, LSD (d-lysergic acid diethylamide) produces characteristic decreases in locomotor activity and investigatory behaviors of rats tested in a novel environment. Because LSD is an agonist at both 5-HT1A and 5-HT2 receptors, however, the respective influences of these different receptors in the behavioral effects of LSD remain unclear. In particular, the paucity of selective 5-HT1A antagonists has made it difficult to assess the specific contribution of 5-HT1A receptors to the effects of LSD. An alternative approach to the delineation of receptor-specific effects is the use of cross-tolerance regimens. In the present studies, rats were pretreated with saline, 8-hydroxy-2(di-n-propylamino)-tetralin (8-OH-DPAT) (0.5 mg/kg SC), 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) (1.0 mg/kg SC), or LSD (60 micrograms/kg SC), every 12 h for 5 or 8 days. Thirty-six hours later, rats were tested in a behavioral pattern monitor 10 min after injection of saline, 0.5 mg/kg 8-OH-DPAT, 1.0 mg/kg DOI, or 60 micrograms/kg LSD. As expected, tolerance to the decreases in locomotor activity produced by acute administrations of 8-OH-DPAT, DOI, or LSD occurred when rats were pretreated chronically with 8-OH-DPAT, DOI, or LSD, respectively. Furthermore, pretreatment with either 8-OH-DPAT or DOI produced cross-tolerance to LSD. These results support the hypothesis that the effects of LSD in this model reflect a combination of 5-HT1A and 5-HT2 effects and support the view that there is an interaction between 5-HT1A and 5-HT2 receptors.
Comparable studies
Other preclinical and animal studies on LSD, most cited first.
Citations in the library
Cited by 19
- Differential contributions of serotonin receptors to the behavioral effects of indoleamine hallucinogens in mice Journal of Psychopharmacology December 8, 2010
- Modulatory effect of the 5-HT1A agonist buspirone and the mixed non-hallucinogenic 5-HT1A/2A agonist ergotamine on psilocybin-induced psychedelic experience European Neuropsychopharmacology January 22, 2016
- Lysergic acid diethylamide (LSD) promotes social behavior through mTORC1 in the excitatory neurotransmission Proceedings of the National Academy of Sciences January 25, 2021
- Differential tolerance to biological and subjective effects of four closely spaced doses of N,N-dimethyltryptamine in humans Biological Psychiatry May 1, 1996
- Effect of Hallucinogens on Unconditioned Behavior Current Topics in Behavioral Neurosciences 2016
and 14 more in the library
Cites 15
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- Do functional relationships exist between 5-HT1A and 5-HT2 receptors? Pharmacology, Biochemistry, and Behavior August 1, 1990
- Lysergic acid diethylamide and 2,5-dimethoxy-4-methylamphetamine are partial agonists at serotonin receptors linked to phosphoinositide hydrolysis. Journal of Pharmacology and Experimental Therapeutics September 1, 1988
- Studies on Lysergic Acid Diethylamide (LSD-25) A M A Archives of Neurology & Psychiatry November 1, 1956
- 5HT-2 mediation of acute behavioral effects of hallucinogens in rats Psychopharmacology March 1, 1990
and 10 more in the library