Dissociation of multiple effects of acute LSD on exploratory behavior in rats by ritanserin and propranolol.
S M Mittman, Mark A. Geyer
Psychopharmacology 1991 DOI: 10.1007/bf02316866 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical experimental study Peer reviewed |
|---|---|
| Population | Rats |
| Interventions | d-lysergic acid diethylamide (LSD) d l-propranolol ritanserin 2 5-dimethoxy-4-iodoamphetamine (DOI) |
| Dose | LSD 60 or 120 micrograms/kg; propranolol 20 mg/kg; ritanserin 2.0 mg/kg; DOI 0.27 mg/kg |
| Duration | 1 h test session |
| Measures | Behavioral Pattern Monitor (BPM) |
| Topics | LSD |
| Key findings | Propranolol blocked LSD's initial suppression of locomotor and exploratory activity, while ritanserin attenuated the later increase in activity; combined treatment prevented both effects. The 5HT-2 agonist DOI produced only initial suppression, blocked by ritanserin, without a later increase. The authors propose that 5HT-1 and 5HT-2 receptor subtypes differentially mediate LSD's biphasic behavioral effects. |
Abstract
Rats tested for 1 h in the Behavioral Pattern Monitor (BPM) after injection of the mixed serotonergic agonist d-lysergic acid diethylamide (LSD) exhibit a behavioral profile similar to that produced by various hallucinogenic 5HT-2 agonists. The characteristic effects of the hallucinogens include suppression of locomotor and exploratory behavior and a preferential decrease in entries into the center of the BPM during the initial half of the test session. After LSD, the initial suppression of responding is followed by a subsequent increase in locomotor activity that is not observed with other serotonergic agonists. In the present studies, the 5HT-1 and beta-adrenergic antagonist d,l-propranolol and the 5HT-2 antagonist ritanserin were administered individually or in combination prior to the acute administration of LSD to test for the involvement of these receptor subtypes in the mediation of the effects of LSD in the BPM paradigm. Propranolol (20 mg/kg) abolished the initial suppression of activity induced by 60 micrograms/kg LSD without affecting the subsequent increase in locomotion. Conversely, 2.0 mg/kg ritanserin failed to block the initial suppressive effects of 60 or 120 micrograms/kg LSD, but attenuated the LSD-induced increases in activity during the second half of the session. The combination of propranolol and ritanserin prevented both these effects of LSD. By contrast, the more selective 5HT-2 agonist 2,5-dimethoxy-4-iodoamphetamine (DOI) (0.27 mg/kg) produced an initial suppression of activity in the BPM that was blocked by 2.0 mg/kg ritanserin and was not followed by a subsequent increase in activity. (ABSTRACT TRUNCATED AT 250 WORDS)
Comparable studies
Other preclinical and animal studies on LSD, most cited first.
Citations in the library
Cited by 28
- The hallucinogenic world of tryptamines: an updated review. Archives of Toxicology August 1, 2015
- Differential contributions of serotonin receptors to the behavioral effects of indoleamine hallucinogens in mice Journal of Psychopharmacology December 8, 2010
- Effect of Hallucinogens on Unconditioned Behavior Current Topics in Behavioral Neurosciences 2016
- Effects of ayahuasca on the development of ethanol-induced behavioral sensitization and on a post-sensitization treatment in mice Physiology & Behavior January 28, 2015
- Repeated lysergic acid diethylamide in an animal model of depression: Normalisation of learning behaviour and hippocampal serotonin 5-HT2 signalling Journal of Psychopharmacology April 30, 2014
and 23 more in the library
Cites 15
- Evidence for 5-HT2 involvement in the mechanism of action of hallucinogenic agents. Life Sciences December 17, 1984
- 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
- 5HT-2 mediation of acute behavioral effects of hallucinogens in rats Psychopharmacology March 1, 1990
- The effects of lysergic acid diethylamide and mescaline-derived hallucinogens on sensory-integrative function: tactile startle. Journal of Pharmacology and Experimental Therapeutics December 1, 1978
- Studies on the Diethylamide of Lysergic Acid (LSD-25) A M A Archives of Neurology & Psychiatry April 1, 1957
and 10 more in the library