Behavioural Pharmacology
June 1, 2019
Susan Schenk, Quenten Highgate
2 citations
Rats trained to recognize a high dose (3.0 mg/kg) of MDMA or amphetamine (0.5 mg/kg) were given drugs that block dopamine or serotonin receptors. Dopamine blockers reduced the rats' ability to recognize amphetamine but not MDMA. Serotonin blockers had no effect on either drug's recognition. The findings suggest that the high-dose MDMA stimulus involves both dopamine and serotonin systems, and either system alone is enough to maintain the drug's effects.
Behavioural Pharmacology
May 6, 2026
Bart A. Ellenbroek, Gernot Riedel
A growing body of evidence shows that psychedelics such as LSD and psilocybin can have long-lasting beneficial effects for treatment-resistant depression, drug and alcohol addiction, and other mental health problems. Ketamine and its S-enantiomer esketamine have been approved for severe, chronic depression. These drugs have unique properties including fast onset of action and, for psilocybin and LSD, very long-lasting effects up to six months or longer after a single administration. This has spurred research in behavioural pharmacology and neuroscience to understand their mode of action. The journal Behavioural Pharmacology is devoting a special issue to this topic and invites submissions of original empirical studies and reviews.
Behavioural Pharmacology
September 25, 2025
Saadet Inan, Paige E. Morris, Scott M. Rawls et al.
Psilocybin, the active compound in Psilocybe mushrooms, reduced pain-related behaviors in adult male rats exposed to formalin-induced noxious stimuli, a model of both acute and persistent inflammatory pain. Doses of 0.1 and 0.3 mg/kg significantly decreased flinching and licking during both early and late pain phases. Pretreatment with volinanserin, a selective blocker of the 5-HT 2A receptor, eliminated this pain-relieving effect, indicating that psilocybin produces analgesia at least partly by activating that receptor.
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
August 21, 2025
Stephen W. White, Tara D. Clover, Kenneth J. Sufka
A synbiotic diet (pre- and probiotics combined) produced antidepressant-like effects in a chick model of treatment-resistant depression, but combining it with ketamine may reduce ketamine's effectiveness. Chicks fed synbiotic feed for 7 days showed fewer distress calls during a depression-like phase after isolation, indicating reduced behavioral despair. However, when given ketamine, chicks on the synbiotic diet showed suppressed distress calls, suggesting a negative interaction between synbiotics and ketamine. The findings are preliminary and indicate that using pre- and probiotic supplements alongside ketamine may produce contradictory effects, warranting further investigation.
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
June 1, 2024
Lawrence M Carey, Saba Ghodrati, Charles P France
Terpenes found in cannabis, such as linalool, limonene, γ-terpinene, and α-humulene, do not produce effects similar to THC or enhance THC's effects in rats. Rats trained to discriminate THC from a vehicle did not respond to terpenes alone as if they were THC, and terpenes did not increase THC's potency; α-humulene actually decreased it. In the tetrad assay, which screens for cannabinoid-like activity, none of the terpenes produced effects in all four components as THC did. The results suggest these terpenes do not act as CB1 receptor agonists in the brain.
Behavioural Pharmacology
June 1, 2022
José Eduardo Suárez-Santiago, Gabriel Roldán Roldán, Ofir Picazo Picazo
Ketamine, an anesthetic that blocks NMDA receptors, can produce symptoms resembling schizophrenia. In mice, five daily injections of ketamine (10 mg/kg) caused memory deficits, anxiety, obsessive-compulsive behaviors, and stereotyped movements. Two experimental drugs targeting the 5-HT6 receptor—an agonist (E-6837) and an antagonist (SB-271046)—each reversed the memory impairment and reduced anxiety when given alone. SB-271046 also decreased climbing behavior. Neither drug affected the light–dark test. Unexpectedly, when either drug was combined with ketamine, anxiety worsened. Both types of 5-HT6 drugs appear to modulate psychotic-like symptoms caused by blocking NMDA receptors.
Behavioural Pharmacology
September 1, 2019
A. Pałucha-poniewiera, K. Podkowa, Andrzej Pilc
Ketamine produces rapid antidepressant effects in people with depression. In rats, a drug called LY341495, which blocks group II metabotropic glutamate receptors, also shows rapid and lasting antidepressant-like activity and can boost the effect of a low dose of ketamine without side effects. This study examined how AMPA receptors and TrkB receptors contribute to the antidepressant-like effects of ketamine (3 mg/kg) given together with LY341495 (0.1 mg/kg) in the forced swim test in rats, measured 40 minutes, 3 hours, and 24 hours after administration. Blocking AMPA receptors with NBQX (10 mg/kg) reversed the antidepressant effect at all time points, while blocking TrkB receptors with ANA-12 blocked the effect only at 3 hours.
Behavioural Pharmacology
October 1, 2017
Alexandre Seillier, Andrea Giuffrida
Social withdrawal in a rat model of schizophrenia is not caused by increased anxiety, according to this study. Rats treated with phencyclidine (PCP) spent less time in social interaction than controls but showed no anxiety-like behaviors in standard tests. Their social deficit was not reduced by repeated exposure to a familiar partner or by the anxiolytic diazepam, but was reversed by the cannabinoid agonist CP55,940, which has anxiogenic properties. The authors conclude that PCP-induced social withdrawal reflects primary negative symptoms (asociality) rather than secondary effects of anxiety, supporting the distinction between primary and secondary negative symptoms in schizophrenia.
Behavioural Pharmacology
September 1, 2016
Mary T. Zanda, Paola Fadda, Cristiano Chiamulera et al.
Methoxetamine (MXE), a novel psychoactive substance sold as a 'legal high,' is chemically similar to ketamine and phencyclidine and acts as a noncompetitive NMDA receptor antagonist. Recent preclinical data show it also stimulates dopamine neurotransmission in the mesolimbic pathway. This review summarizes MXE's behavioral and toxicological effects, its pharmacology, and the frequent adverse effects seen in a growing number of intoxications. The review notes that MXE's potential rapid antidepressant activity, suggested by its similarity to ketamine and supported by recent preclinical findings, requires further investigation.
Behavioural Pharmacology
April 1, 2016
Cristiano Chiamulera, Federica Armani, Anna Mutti et al.
Methoxetamine (MXE), a chemical analogue of ketamine, fully substitutes for ketamine in a drug discrimination test in rats, indicating shared subjective and potentially addictive properties. Rats trained to distinguish ketamine from a placebo generalized the ketamine stimulus to MXE and to the NMDA channel blocker MK-801, but only partially to lysergic acid and methamphetamine. The highest dose of lysergic acid produced 77.7% generalization. These results suggest that evaluating novel ketamine-like drugs should consider not only chemical and molecular similarities but also overlapping psychopharmacological effects.
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.