European Journal of Pharmacology
July 19, 2026
Yongning Lv, Zihe Yang, Linjie Li et al.
Intranasal ketamine given twice weekly for two weeks to rats exposed to chronic stress improved depressive-like behaviors, restored hypothalamic neuronal structure, increased synaptic density, and enhanced mitochondrial ultrastructure. RNA sequencing and molecular validation identified increased expression of Ndufa10, a gene encoding a mitochondrial complex I subunit, and its protein NDUFA10 in the hypothalamus. Blocking mitochondrial complex I with rotenone reduced these behavioral and molecular effects, suggesting that mitochondrial complex I activity contributes to ketamine's antidepressant-like actions. α-Synuclein protein changed in parallel without corresponding mRNA changes, indicating a post-transcriptional alteration.
European Journal of Pharmacology
June 1, 2026
Gianluca Lavanco, Valentina Castelli, Cesare D'Amico et al.
Long-chain omega-3 polyunsaturated fatty acids (LC-ω-3-PUFAs) given during pregnancy and lactation prevented memory deficits caused by prenatal THC exposure in adolescent rats. THC exposure during gestation impaired hippocampus-dependent memory and disrupted excitatory/inhibitory balance in a sex-dependent manner. Supplementation with an omega-3-enriched diet restored memory performance in both sexes. In males, the fatty acids counteracted THC-induced synaptic hyperexcitability by normalizing expression of plasticity markers and endocannabinoid enzymes. In females, they rebalanced a THC-induced inhibitory shift by reducing certain synaptic protein and enzyme levels. The findings suggest perinatal omega-3 supplementation is a safe nutritional strategy to protect against THC-induced neurodevelopmental harm by restoring endocannabinoid system balance and supporting sex-specific brain plasticity.
European Journal of Pharmacology
April 5, 2024
Stanislav Rozov, Roosa Saarreharju, Stanislav Khirug et al.
Inhaling 50% nitrous oxide for one hour and a single low dose of ketamine both alter the activity of genes that regulate mitogen-activated protein kinases in the medial prefrontal cortex of adult mice, particularly in pyramidal cells. Nitrous oxide produced much larger and more widespread changes in gene expression than ketamine. Ketamine increased the firing rate of putative pyramidal neurons and boosted gamma brain wave activity, whereas nitrous oxide did not. The findings suggest that the two drugs share a common molecular target but cause different immediate electrical changes in the brain.
European Journal of Pharmacology
November 1, 2022
Júlia Grigorini Mori Ayub, C. Tosta, Breno Lopes Macedo et al.
Female mice are less sensitive than male mice to the anti-compulsive-like effect of S-ketamine, both when used alone and as an adjuvant to fluoxetine. S-ketamine reduced compulsive-like behavior in female mice only at a dose of 30 mg/kg, whereas the effective dose in male mice is 10 mg/kg. Combining sub-effective doses of S-ketamine and fluoxetine reduced marble-burying behavior in both sexes, but male mice showed a better response. Variations in female sex hormones (estrogen and progesterone), inferred from the estrous cycle and ovariectomy, did not influence S-ketamine's effect.
European Journal of Pharmacology
August 15, 2019
Jason Wallach, Tristan Colestock, Julià Agramunt et al.
Fluorolintane, a 1,2-diarylethylamine sold as a 'research chemical' for dissociative effects, was studied pharmacologically for the first time alongside five related isomers. In vitro binding showed fluorolintane has high affinity for NMDA receptors (Ki = 87.92 nM) and even higher affinities for dopamine transporters (DAT) in most cases. Functional experiments in rat hippocampal slices demonstrated that fluorolintane inhibits NMDA receptor-induced field excitatory postsynaptic potentials and blocks long-term potentiation, consistent with NMDA receptor antagonism. In rats, fluorolintane disrupted prepulse inhibition (a measure of sensorimotor gating) with a median effective dose of 13.3 mg/kg, supporting anecdotal reports of dissociative effects in humans.
European Journal of Pharmacology
April 5, 2017
James Oluwagbamigbe Fajemiroye, Polepally Reddy Prabhakar, Luiz Carlos da Cunha et al.
A derivative of the hallucinogen salvinorin A, called 22-azidosalvinorin A (SA2), shows antidepressant-like effects in mice. Oral treatment with SA2 at doses of 5, 10, and 20 mg/kg reduced immobility in the forced swimming test and tail suspension test without affecting general locomotion, indicating an antidepressant-like property. This effect was not blocked by serotonin depletion or a 5-HT1A receptor antagonist, but was blocked by depleting catecholamines or blocking α1-adrenoceptors. SA2 mildly inhibited monoamine oxidase and showed affinity for α1A, α1B, α1D, and κ-opioid receptor subtypes, suggesting its antidepressant-like action is mediated through monoamine systems.
European Journal of Pharmacology
November 15, 2013
Aashish S Morani, Amy W M Ewald, Katherine M Prevatt-Smith et al.
Activating the κ opioid receptor with the salvinorin A analogue 2-methoxy-methyl salvinorin B (MOM Sal B) at 0.3 mg/kg reduced cocaine-seeking behavior in rats, but also reduced sucrose reinforcement. No sedation was observed—locomotion in cocaine-induced hyperactivity and open field tests was unchanged—yet the forced swim test showed increased immobility and decreased swimming times, indicating pro-depressive effects. The compound thus modulates cocaine-seeking non-selectively without sedation, but depressive side effects may limit its therapeutic use.
European Journal of Pharmacology
July 11, 2005
Kinzo Matsumoto, Ryo Morishige, Yukihisa Murakami et al.
Isorhynchophylline, a compound from Uncaria plants used in traditional Chinese medicine, preferentially blocks 5-HT2A receptors in the brain, likely through competitive antagonism. In mice, it dose-dependently reduced 5-HT2A-mediated head-twitch responses without affecting 5-HT1A or 5-HT2C behaviors. A related alkaloid, isocorynoxeine, had similar effects, while stereoisomers did not, indicating the oxindole moiety's configuration is essential for this activity.
European Journal of Pharmacology
June 29, 2001
M Narita, K Yoshizawa, M Nomura et al.
Ketamine, an NMDA receptor antagonist used as an anesthetic, can produce psychotomimetic effects like nightmares and hallucinations with chronic use. In Fischer 344 rats trained to discriminate ketamine (5 mg/kg) from saline, non-competitive NMDA receptor antagonists that block NR2A- and NR2B-containing receptors (phencyclidine, dizocilpine) and an NR2A-preferring antagonist (dextromethorphan) fully substituted for the ketamine cue in a dose-dependent manner. The NR2B-selective antagonist ifenprodil, the competitive NMDA antagonist CPP, and the sigma receptor ligand DTG did not generalize. The findings suggest that antagonism of NR1/NR2A-containing NMDA receptors may be critical for producing ketamine's discriminative stimulus effects.
European Journal of Pharmacology
April 13, 2001
T Habara, T Hamamura, M Miki et al.
The selective 5-HT2A receptor antagonist M100907 attenuates phencyclidine (PCP)-induced Fos expression in specific rat brain regions. PCP (5 mg/kg) induced Fos expression in the cingulate cortex area 3, agranular insular cortex, piriform cortex, nucleus accumbens, anterior paraventricular thalamic nucleus, and ventral lateral septal nucleus. Pretreatment with M100907 (0.5 mg/kg) reduced Fos expression in the nucleus accumbens core and shell, agranular insular cortex, and piriform cortex, but not in other regions. M100907 alone did not induce Fos expression in any region, including the dorsolateral caudate/putamen. These results indicate that 5-HT2A receptor antagonism attenuates Fos expression in a regionally specific manner in the PCP model of psychosis.
European Journal of Pharmacology
August 29, 1996
T Suzuki, T Yamamoto, T Hori et al.
The binding properties and brain distribution of a radioactive form of the compound 3-OH-PCP, a derivative of phencyclidine (PCP), were examined in rat brain tissue using autoradiography. Binding occurred with fast and slow components, and the pattern of binding matched that of other PCP receptor labels, TCP and MK-801. Highest binding was in the hippocampus and outer cerebral cortex layers, while low binding was in the brain stem and cerebellum. The binding was strongly blocked by MK-801 and 3-OH-PCP, but less so by a related compound, (+)-SKF 10047, in certain brain regions. Antagonists of the NMDA receptor complex also displaced binding similarly to MK-801, indicating the binding site is essentially the same as the PCP site labeled by TCP and MK-801.
European Journal of Pharmacology
October 1, 1984
M D Hynes, D L Hymson
Nitrous oxide, an analgesic and anesthetic gas, produces subjective effects in rats that resemble those of psychotomimetic drugs rather than morphine. Rats trained to discriminate ethylketocyclazocine, a psychotomimetic opioid, generalized the cue to nitrous oxide in a concentration-dependent manner, while rats trained to discriminate morphine did not generalize even at 80 percent nitrous oxide. The narcotic antagonist naltrexone did not block this generalization. These findings align with human studies and suggest that nitrous oxide, despite sharing some analgesic properties with morphine, has distinct subjective effects similar to psychotomimetic substances.