European Journal of Pharmacology
April 7, 1992
C W Callaway, M A Geyer
35 citations
Injecting S-MDMA (a form of MDMA, or ecstasy) directly into a brain region called the nucleus accumbens made rats more active, similar to the effect of amphetamine. Blocking serotonin with fluoxetine did not prevent this hyperactivity, even though it blocks the effects of systemically given S-MDMA. A drug that only releases serotonin, MBDB, did not increase activity when injected into the nucleus accumbens, though it does when given systemically. These results suggest that S-MDMA's effects in the nucleus accumbens are due to its ability to release catecholamines like dopamine, not serotonin, and differ from its systemic actions.
European Journal of Pharmacology
January 1, 1989
James B. Appel, Patrick M. Callahan
34 citations
Rats trained to distinguish mescaline (10 mg/kg) from saline showed that the mescaline cue generalized to high doses of the 5-HT2 agonists DOM, LSD, and psilocybin, while generalization to 5-HT1 agonists was unclear. The mescaline cue was blocked by high doses of 5-HT2 antagonists (ketanserin, LY-53857, pirenperone) but not by less selective serotonin (metergoline) or dopamine (SCH-23390, haloperidol) antagonists. These results suggest that 5-HT2 receptors are involved in the stimulus properties of mescaline.
European Journal of Pharmacology
November 2, 1993
M D Schechter, T L Gordon
33 citations
Rats were trained to distinguish the effects of ibogaine, a hallucinogenic alkaloid used in West Central Africa and studied for treating chemical dependency, from a placebo. Ibogaine from three different suppliers (Sigma Chemical Co., the National Institute on Drug Abuse, and NDA International Inc.'s Endabuse) produced similar discrimination in the rats, with effective doses ranging from 2.5 to 3.4 mg/kg. Other drugs tested, including those affecting dopamine and serotonin systems, did not produce ibogaine-like effects. The findings suggest that ibogaine from these sources is comparable for preclinical research.
European Journal of Pharmacology
June 2, 1994
D Marona-Lewicka, D E Nichols
32 citations
MMAI (5-methoxy-6-methyl-2-aminoindan) appears to be a selective serotonin releaser without psychostimulant or hallucinogenic effects. In rats trained to discriminate MMAI from saline, only other serotonin-releasing drugs fully mimicked MMAI's effects. MMAI did not produce amphetamine-like or LSD-like stimulus effects. Depleting serotonin with p-chlorophenylalanine blocked MMAI's discriminative cue for about a week, and selective serotonin reuptake inhibitors reduced its discriminability. Behavioral observations showed MMAI induced a syndrome similar to that caused by serotonin precursors or receptor agonists, including hypolocomotion, catalepsy-like posture, and flat body posture. The findings suggest MMAI acts primarily by releasing serotonin rather than directly activating or blocking neurotransmitter receptors.
European Journal of Pharmacology
February 13, 1990
L Cancela, M Volosin, V A Molina
31 citations
Rats immobilized for 2 hours daily over 7 days developed a heightened behavioral response to a serotonin receptor agonist, 5-MeODMT, measured by forepaw treading and hind-limb abduction. Giving naloxone before each stress session fully blocked this increased reactivity. Conversely, pairing morphine or beta-endorphin with immobilization for 3 days produced an even stronger response than immobilization alone. Chronic immobilization did not affect shaking behavior induced by another serotonin precursor, 5-HTP. These findings suggest chronic stress selectively adapts the 5-HT1 serotonin site and activates an opioid mechanism likely involved in that adaptation.
European Journal of Pharmacology
November 21, 2005
Vishal Panchal, Olga D Taraschenko, Isabelle M Maisonneuve et al.
30 citations
18-Methoxyroconaridine (18-MC), a synthetic derivative of ibogaine, reduces morphine self-administration and alleviates several signs of acute opioid withdrawal in rats. The mechanism behind 18-MC's attenuation of opioid withdrawal was unknown. In vitro studies show 18-MC is a potent antagonist of alpha3beta4 nicotinic receptors, predominantly located in the medial habenula and interpeduncular nuclei. To test whether brain areas with high densities of these receptors are involved, 18-MC was locally administered into the medial habenula, interpeduncular nucleus, and locus coeruleus of morphine-dependent rats, followed by naltrexone to precipitate withdrawal.
European Journal of Pharmacology
September 3, 1984
A P Nisbet, C A Marsden
29 citations
Destroying serotonin-producing neurons in the brain with a chemical (5,7-DHT) made rats more sensitive to a drug that activates serotonin receptors (5-MeO-DMT). The stronger behavioral response matched how much serotonin was lost. But the same treatment did not increase the hyperactivity caused by a different drug (RU-24969) that targets a specific serotonin receptor subtype (5HT1). This suggests that different serotonin receptors control different behaviors and that losing serotonin neurons changes sensitivity to some, but not all, receptor-activating drugs.
European Journal of Pharmacology
January 20, 1987
T Nabeshima, K Ishikawa, K Yamaguchi et al.
27 citations
Withdrawal from chronic methysergide, a 5-HT2 receptor blocker, potentiates phencyclidine (PCP)-induced head-twitch behavior in rats, while repeated PCP treatment leads to tolerance that is blocked by methysergide. PCP-induced behaviors (head-twitch, head-weaving, turning, backpedalling) were attenuated after 12 days of daily PCP, but head-twitch increased significantly after stopping methysergide. Binding studies showed increased Bmax of 5-HT2 and PCP receptors after methysergide withdrawal, and decreased Bmax of 5-HT2 receptors after PCP tolerance, with no affinity changes. PCP displaced [3H]ketanserin at 5-HT2 but not [3H]5-HT at 5-HT1 sites, indicating PCP produces head-twitch through agonistic action at 5-HT2 receptors.
European Journal of Pharmacology
June 3, 1983
B L Jacobs, J Heym, K Rasmussen
25 citations
In unanesthetized and unrestrained cats, serotonergic neurons in several raphe nuclei showed a strong negative correlation between their spontaneous firing rate during waking and their response to systemic injections of the serotonin agonists 5-MeODMT or LSD. The authors propose that both the baseline activity of these neurons and the size of their response to serotonin-like drugs can be explained by the density of autoreceptors on each neuron.
European Journal of Pharmacology
December 15, 2006
Roman Paškulin, Polona Jamnik, Marko Živin et al.
24 citations
Ibogaine, an alkaloid from the Tabernanthe iboga plant, reduces withdrawal symptoms in animal models of drug addiction, and its effects outlast its presence in the body, suggesting lasting metabolic changes. In rats given a single 20 mg/kg dose, brain protein analysis at 24 and 72 hours revealed increased levels of key energy-metabolism enzymes: glyceraldehyde-3-phosphate dehydrogenase, aldolase A, pyruvate kinase, and malate dehydrogenase. These enzymes are involved in glycolysis and the tricarboxylic acid cycle. The findings indicate that ibogaine's anti-addiction effects may arise from enhanced energy availability, supporting cellular changes needed for detoxification and reversal of drug tolerance.
European Journal of Pharmacology
May 7, 2021
D. Fonseca, D. M. Ribeiro, Margarida Tapadas et al.
23 citations
MDMA, also known as ecstasy, increases blood pressure and heart rate and can impair cardiac contractile function, cause arrhythmias, myocardial necrosis, and valvular heart disease, as well as vasoconstriction, disrupt vascular integrity, and alter haemostasis. These effects involve interactions with monoamine transporters and receptors, oxidative stress, and activation of matrix metalloproteinases. The review describes both the cardiovascular risks of recreational MDMA use and the unresolved risk/benefit ratio for its therapeutic use in psychiatry, especially in patients with underlying cardiovascular disease.
European Journal of Pharmacology
February 25, 2000
M E Alburges, B P Ramos, L Bush et al.
21 citations
Ibogaine, a compound from the West African shrub Tabernanthe iboga, and cocaine both increased substance P—a key signaling molecule—in brain regions associated with movement and reward, specifically the striatum and substantia nigra, 12 hours after the last drug treatment. Substance P levels were not significantly raised in the nucleus accumbens by either drug. These increases were blocked by antagonists of dopamine D1 or D2 receptors, indicating involvement of dopamine pathways. Unlike cocaine, multiple doses of ibogaine did not raise substance P in the frontal cortex. The findings suggest substance P systems may contribute to the effects of ibogaine and cocaine.
European Journal of Pharmacology
July 7, 1988
P C Moser, P H Redfern
21 citations
Four benzodiazepines (diazepam, clonazepam, oxazepam, and clobazam) potentiated head-twitch responses in mice induced by directly acting serotonin receptor agonists (5-MeODMT, quipazine, mescaline) but not by the indirectly acting agonist 5-HTP, which was sometimes inhibited. The potentiation of 5-MeODMT by clonazepam (10 mg/kg) was not blocked by flumazenil, bicuculline, or serotonin depletion, nor mimicked by muscimol (which inhibited head-twitches). These findings suggest the potentiation occurs postsynaptically and is not mediated by benzodiazepine receptors. Failure to potentiate 5-HTP responses likely results from reduced serotonin neuronal activity via benzodiazepine receptors, since co-administration of flumazenil and clonazepam potentiated 5-HTP effects while each alone had no effect.
European Journal of Pharmacology
December 1, 1983
Michael E. Trulson, Terriann Crisp, Leslie J. Henderson
21 citations
Pretreating cats with low doses of either a serotonin antagonist (methysergide) or a dopamine antagonist (haloperidol) nearly completely blocked the characteristic behavioral effects of mescaline. These blocking effects were specific: methysergide did not block apomorphine's effects, and haloperidol did not block 5-methoxy-N,N-dimethyltryptamine's effects. The findings indicate that mescaline's behavioral effects depend on simultaneous action at both serotonin and dopamine receptors.
European Journal of Pharmacology
July 30, 1982
J Heym, G F Steinfels, B L Jacobs
21 citations
In freely moving cats, neurons in the dorsal raphe nucleus (DRN) are much more sensitive to the psychedelic compounds 5-MeO-DMT and LSD than neurons in the nucleus raphe pallidus (NRP). Low, behaviorally effective doses of these drugs strongly suppress activity in DRN neurons, while NRP neurons remain largely unaffected. This differential sensitivity suggests a unique autoregulatory control mechanism within distinct brain regions, where serotonin-producing neurons respond differently depending on their neuroanatomical location.
European Journal of Pharmacology
December 17, 1981
R A Glennon, J A Rosecrans, R Young
21 citations
Rats learned to distinguish an injection of the hallucinogen 5-methoxy-N,N-dimethyltryptamine (5-OMe DMT) from saline in a two-lever drug discrimination task. Once they reliably identified the drug, 36 different phenylisopropylamine compounds were tested to see if they produced similar effects. The compounds fell into three groups: those that fully mimicked 5-OMe DMT, those that partially did, and those that did not. The findings suggest that certain phenylisopropylamines, unlike amphetamine, can produce hallucinogen-like effects in rats, likely involving serotonin pathways.
European Journal of Pharmacology
October 8, 1997
I M Maisonneuve, K E Visker, G L Mann et al.
20 citations
Ibogaine and two related compounds (noribogaine and 18-methoxycoronaridine) both inhibit and later enhance cocaine-induced hyperactivity in rats, depending on timing. When given 1 hour before cocaine, all three agents reduced the hyperactivity caused by cocaine. When given 19 hours before cocaine, they instead amplified it. These opposite, time-dependent effects explain conflicting findings in earlier research and were not caused by the drugs' own effects on movement.
European Journal of Pharmacology
December 19, 1996
A S Schneider, J E Nagel, S J Mah
20 citations
Low concentrations of ibogaine (1-10 microM) selectively inhibit nicotinic receptor-mediated catecholamine release in cultured chromaffin cells, while higher concentrations (100 microM) block additional modes of release. This suggests ibogaine acts at the nicotinic acetylcholine receptor, possibly at the ion channel site, clarifying one mechanism underlying its putative anti-addictive properties.
European Journal of Pharmacology
November 25, 1983
R A Shephard, P L Broadhurst
20 citations
In rats selectively bred for avoidance learning, the drug 5-MeODMT (2.5 mg/kg) reduced feeding in a novel environment, while diazepam (1 mg/kg), methysergide, and 1-propranolol (6 mg/kg) increased it; d-propranolol had no effect. Roman Low Avoidance rats were most sensitive to all drugs and showed the strongest neophobia. Female Roman High and Control Avoidance rats were more sensitive to 5-MeODMT than males. These strain and sex differences suggest links between arousal, biochemical traits, and drug responsiveness.
European Journal of Pharmacology
June 3, 1983
O G Berge, D Chacho, K Hole
20 citations
5-MeO-DMT, a psychedelic compound, inhibits the reuptake of serotonin in rat brain tissue at concentrations between 0.5 and 500 micromolar, affecting the striatum, hippocampus, and hypothalamus. At higher concentrations (10 micromolar), it also inhibits dopamine reuptake and triggers the release of both serotonin and dopamine from nerve endings. These findings suggest that 5-MeO-DMT's effects as a serotonin agonist may involve blocking reuptake, not just directly stimulating receptors as previously thought.
European Journal of Pharmacology
June 16, 2000
K K Szumlinski, I M Maisonneuve, S D Glick
19 citations
Ibogaine, given to rats 19 hours before a cocaine challenge, reversed a key brain change caused by repeated cocaine use: the sensitized dopamine response in the nucleus accumbens. While ibogaine did not alter the dopamine increase from a single cocaine dose, it eliminated the amplified dopamine release that normally occurs in cocaine-sensitized animals. This effect on neuroadaptation may underlie ibogaine's proposed anti-addictive properties.
European Journal of Pharmacology
July 1, 2019
D. Luethi, R. Widmer, D. Trachsel et al.
18 citations
Certain ring-substituted phenethylamines produce psychedelic effects mainly through serotonin 5-HT2A receptors. 2C-BI derivatives, a class of 4'-aryl substituted 2,5-dimethoxyphenethylamines, were tested for binding and activity at monoamine receptors and transporters. Several 2C-BI compounds bound strongly to human serotonergic and adrenergic receptors and to rat and mouse trace amine-associated receptor 1. 2C-BI-8 and 2C-BI-12 activated serotonin 5-HT2A and 5-HT2B receptors at submicromolar concentrations, while only 2C-BI-1 and 2C-BI-7 activated human trace amine-associated receptor 1. 2C-BI-3 and 2C-BI-4 interacted weakly with monoamine transporters. The high affinities at the 5-HT2A receptor suggest a sterically tolerant binding pocket, and potent partial activation by 2C-BI-8 and 2C-BI-12 indicates potential psychedelic effects similar to other 2C compounds.
European Journal of Pharmacology
January 15, 1985
M E Trulson, G F Keltch
18 citations
Repeated doses of the psychedelic compound 5-MeODMT in rats rapidly produced tolerance to its behavioral effects, with the effective dose doubling and the duration of the syndrome dropping from about 15 minutes to just over 1 minute. This tolerance completely vanished within 4 hours after stopping treatment. The effect was not caused by changes in how much drug entered the brain, but appeared to result from reduced binding of the drug to serotonin receptors. These findings contradict earlier reports that claimed no tolerance develops to 5-MeODMT.
European Journal of Pharmacology
December 5, 1996
R A Rabin, J C Winter
17 citations
Ibogaine and its metabolite noribogaine do not directly alter adenylyl cyclase activity in the rat brain, but they enhance the inhibition of this enzyme caused by morphine and serotonin. In the frontal cortex, midbrain, and striatum, both compounds amplified morphine's effect; in the hippocampus, they boosted serotonin's effect. Ibogaine was more potent than noribogaine, but both were equally effective. The compounds did not affect inhibition by the muscarinic agonist carbachol. This selective potentiation of receptor-mediated inhibition may contribute to ibogaine's pharmacological actions.
European Journal of Pharmacology
July 9, 1987
T Nabeshima, K Ishikawa, K Yamaguchi et al.
17 citations
Ritanserin, a drug that blocks serotonin 5-HT2 receptors, reduced head-twitch behavior in mice caused by phencyclidine (PCP) and another serotonin-like drug, but increased head-weaving behavior. The two behaviors were inversely related. Depleting serotonin with PCPA reduced head-weaving caused by PCP plus ritanserin but not head-weaving caused by the serotonin-like drug. These results suggest PCP causes head-weaving by indirectly activating a different serotonin receptor (possibly 5-HT1) after releasing serotonin, and head-twitch by directly activating 5-HT2 receptors.