Behavioural pharmacology
April 1, 2019
Kevin Sean Murnane
84 citations
Serotonin is an ancient neurotransmitter found throughout the brain, but its specific functions remain debated. This review argues that stress, especially from danger or existential threats, increases the activity of the 5-HT2A serotonin receptor subtype. This upregulation is proposed as an adaptive mechanism to enhance learning and avoidance of danger by forming associations with environmental cues signaling threat. The system may contribute to PTSD symptoms during life-threatening situations. The drug MDMA, which activates 5-HT2A receptors, has shown success in treating PTSD and is suggested to paradoxically work through these same receptors to alleviate symptoms. The central claim is that serotonin acts as a stress detection and response system.
Behavioural pharmacology
December 1, 2005
William E Fantegrossi, Kelly M Kugle, Leander J Valdes et al.
80 citations
Salvinorin A, a natural compound from the Mexican mint Salvia divinorum, is the first known naturally occurring kappa-opioid receptor agonist with a novel chemical structure distinct from other opioids. In mice, salvinorin A caused rapid but short-lived sedation and motor incoordination, similar to the effects of the mu-agonist remifentanil and the synthetic kappa-agonist U69,593. Using selective antagonists, the motor effects of salvinorin A and U69,593 were shown to be mediated by kappa-opioid receptors, while remifentanil's effects involved mu-receptors. Salvinorin A and U69,593 differed in their susceptibility to antagonism by nor-binaltorphamine, suggesting salvinorin A may bind to the kappa-receptor differently than traditional kappa-agonists. This raises the possibility that developing other diterpene-based opioids could yield therapeutic compounds.
Behavioural pharmacology
October 1, 2012
Mitchell T Harden, Staci E Smith, Jennifer A Niehoff et al.
37 citations
Salvinorin A (SalvA), a compound from the plant Salvia divinorum that activates κ-opioid receptors, may have antidepressant effects. In a study using male and female Long-Evans rats, chronic mild stress (CMS) for three weeks reduced their preference for sucrose water, indicating anhedonia, a key symptom of depression. After three more weeks of CMS, rats given daily injections of 1 mg SalvA per kilogram of body weight showed a reversal of this anhedonia, while control rats did not. Nonstressed rats given the same dose showed no change in sucrose preference. The findings suggest that chronic SalvA treatment acts as an effective antidepressant in this animal model.
Behavioural pharmacology
September 1, 2011
Mary Melissa Peet, Lisa E Baker
21 citations
Two synthetic derivatives of salvinorin A, EOM-Sal B and MOM-Sal B, fully substituted for salvinorin A in rats trained to discriminate the drug, and both were more potent than the parent compound. EOM-Sal B also produced effects that lasted longer than salvinorin A. Morphine and one hallucinogen failed to substitute, but ketamine and LSD partially substituted. The findings suggest that these derivatives produce similar stimulus effects to salvinorin A, which are distinct from other drug classes, and warrant further study.
Behavioural pharmacology
August 1, 2000
C Zubaran, M Shoaib, I P Stolerman
7 citations
Ibogaine, a naturally occurring psychoactive alkaloid reported to block nicotinic receptors, was tested for its ability to alter sensitization to nicotine's locomotor stimulant effect in rats. Over 21 days, rats received daily co-administration of ibogaine (0, 5, or 10 mg/kg) with nicotine (0 or 0.4 mg/kg). Nicotine alone produced clear sensitization—enhanced locomotor activity upon repeated exposure—but co-administration of ibogaine did not affect the degree of sensitization. Ibogaine alone (5–20 mg/kg) did not influence locomotor activity and did not alter the expression of the already-sensitized response to nicotine. The results provide no evidence that ibogaine retards or suppresses sensitization to nicotine.
Behavioural pharmacology
April 1, 2025
Eghbal Jasemi, Ali Razmi, Salar Vaseghi et al.
5 citations
In mice, early maternal separation caused depressive-like and anxiety-like behaviors, reduced movement, and altered hippocampal gene expression and methylation of Slc6a4 and Nr3c1. A single injection of Psilocybe cubensis extract (20 mg/kg) on postnatal day 60 reversed these behavioral and molecular changes. The extract appears to influence serotonergic signaling and stress response pathways by modifying Slc6a4 and Nr3c1 expression and methylation. These findings suggest that compounds from Psilocybe cubensis may counteract some long-term effects of early-life stress.
Behavioural pharmacology
June 1, 2025
Ronan Depoortère, Mariusz Papp, Piotr Gruca et al.
2 citations
Ketamine rapidly reverses depression-like symptoms in rats exposed to chronic mild stress, including loss of pleasure and working memory deficits, when given systemically or directly into the prefrontal cortex. Blocking serotonin 5-HT1A receptors in the prefrontal cortex with WAY-100635 prevents these effects, showing that ketamine's rapid antidepressant and pro-cognitive actions require activation of these receptors. The findings suggest that drugs directly targeting prefrontal cortex 5-HT1A receptors could provide rapid antidepressant effects and improve cognitive deficits without ketamine's side effects or need for clinical supervision.
Behavioural pharmacology
October 1, 2024
David R Maguire
2 citations
A 5-HT2A receptor agonist called DOM, tested in four rhesus monkeys using a choice procedure, showed neither rewarding nor punishing effects. When monkeys chose between a sucrose pellet alone or a pellet plus an intravenous infusion, fentanyl increased choice for the infusion (rewarding), while histamine decreased it (punishing). DOM, tested across doses of 3.2 to 100 µg/kg/infusion, did not systematically alter choice, whether given before or after histamine. This suggests DOM lacks both positive reinforcing and aversive properties under conditions sensitive to these effects.
Behavioural pharmacology
July 7, 2025
Kaixi Li, Nan Li, Yuanyuan Chen et al.
Three synthetic tryptamines—AMT, 5-MeO-AMT, and 5-MeO-DiPT—showed acute toxic effects, reduced movement, and triggered head-twitch responses (a sign of hallucinogenic-like behavior) in mice. Pretreatment with a low dose of M100907, a 5-HT2A receptor antagonist, blocked the head-twitch responses caused by all three substances. The findings indicate these compounds are toxic, inhibit locomotor activity, and have hallucinogenic properties, providing experimental data to support future regulation and mechanistic research.
Behavioural pharmacology
April 1, 2025
Danielle Nykanen, Hannah Stiffler, Merrick Bay et al.
Cannabinoid agonism via WIN 55,212-2 did not impair auditory discrimination in rats. Twenty-two rats were trained to press a lever for sucrose in response to either a pure tone or white noise, with correct responses reinforced and incorrect ones punished. After reaching criterion, they received 1.2 mg/kg, 3 mg/kg, or saline. On day 3, active lever-pressing was higher in both dose groups compared to saline, but overall pressing decreased over time in the high-dose group. No effects on discrimination or errors were observed, indicating that cannabinoid agonism did not negatively affect auditory discrimination, contrary to some previous findings.
Behavioural pharmacology
February 1, 2014
Kellianne J Richardson, Keith L Shelton
Nitrous oxide (N₂O) gas produces abuse-related behavioral effects that may differ from other inhalants. In a drug discrimination experiment, 16 mice were trained to distinguish between 10-minute exposure to 60% N₂O mixed with oxygen and pure oxygen. Mice learned this discrimination in 40 days. N₂O itself fully substituted for the training condition in a concentration-dependent manner, with full substitution requiring 7 minutes of exposure. The aromatic hydrocarbon toluene almost fully substituted for N₂O, while other compounds like 1,1,1-trichloroethane, methoxyflurane, isoflurane, and ethanol showed lesser substitution. D-amphetamine and the odorant 2-butanol did not substitute. The varying degrees of incomplete substitution suggest that N₂O's discriminative stimulus properties—and likely its subjective effects in humans—are probably not unique, though its overall effects may include novel components.
Behavioural pharmacology
February 1, 2005
J Podhorna, M Didriksen
To create an animal model of cognitive deficits seen in schizophrenia, researchers tested various doses and schedules of the drug phencyclidine (PCP) in male mice and rats performing a spatial water maze task. A 10-day pre-treatment period prevented PCP-induced motor problems in mice, while 3 days sufficed for rats. PCP impaired spatial learning only when given before daily training trials, not when given immediately after. The optimal dose for producing cognitive impairment with minimal side effects was 2.5 mg/kg. Results indicate PCP disrupts learning and possibly retrieval but not the consolidation of new information.
Behavioural pharmacology
February 1, 1992
C.S. Dohrn, J.L. Lichtor, R.S. Finn et al.
In 12 healthy volunteers, inhaling 20% and 40% nitrous oxide produced robust mood changes, including confusion, sedation, euphoria, dysphoria, and stimulation during inhalation, with fatigue, depression, and anxiety increasing after 40% nitrous oxide stopped. Performance on the Digit Symbol Substitution Test was significantly impaired during 40% nitrous oxide but recovered quickly. Sex differences in subjective effects emerged. Eight of 12 subjects liked the 40% concentration, one was neutral, and three disliked it. Peak effect ratings were dose-related.