Pharmacology, biochemistry, and behavior
January 1, 1991
S Ahlenius, K Larsson
31 citations
A dose of 5-MeODMT, a serotonin receptor agonist, reduced the number of intromissions before ejaculation and shortened ejaculation latency in male rats, indicating facilitated sexual behavior. This effect was blocked by pindolol, a 5-HT1 receptor antagonist, but not by pirenperone or metergoline, which block 5-HT2 receptors. In contrast, 5-HTP, a serotonin precursor, increased mounts and intromissions and lengthened ejaculation latency, an effect that was additive with pindolol. Betaxolol had no effect alone or with 5-HTP. The findings suggest that stimulating 5-HT1 receptors facilitates male rat sexual behavior, while stimulating 5-HT2 receptors inhibits it.
Pharmacology, biochemistry, and behavior
January 1, 1981
R F Schlemmer, J M Davis
31 citations
Dopamine systems help regulate submissive behavior in Stumptail macaques. Chronic administration of d-amphetamine (3.2 mg/kg/day for 12 days) significantly increased submissive gestures in some treated monkeys, even without a concurrent increase in aggression from others. This effect was blocked by haloperidol and pimozide, drugs that block dopamine receptors. The dopamine agonist apomorphine caused a large, dose-dependent increase in submissive gestures; repeated apomorphine (1.0 mg/kg/day for 12 days) produced a similar increase to amphetamine in monkeys previously treated with amphetamine. The hallucinogen 5-methoxy N,N-dimethyltryptamine also increased submissive gestures via dopamine systems, as dopamine blockers antagonized this response while serotonin antagonists did not. These findings may relate to drug-induced and endogenous psychopathologies in humans.
Pharmacology, biochemistry, and behavior
January 1, 2001
K K Szumlinski, R E Haskew, M Y Balogun et al.
28 citations
Pretreatment with ibogaine or its synthetic derivative 18-methoxycoronaridine reversed the behavioral disinhibition and increased corticosterone levels caused by a low dose of methamphetamine in rats. Methamphetamine alone increased open-arm entries in the elevated plus maze and raised plasma corticosterone, suggesting behavioral disinhibition rather than anxiety reduction. Both iboga compounds blocked these effects without altering general locomotion, indicating a potential mechanism for their anti-addictive properties through modulation of neuroendocrine stress responses.
Pharmacology, biochemistry, and behavior
December 1, 1992
P A Palumbo, J C Winter
26 citations
Ibogaine's effects were tested in rats trained to discriminate yohimbine, DOM, or LSD from no treatment. Ibogaine did not significantly mimic yohimbine, but it partially mimicked DOM and LSD. Pizotyline blocked these effects, suggesting ibogaine's stimulus properties involve 5-HT2 receptor activity, with a possible 5-HT1A contribution.
Pharmacology, biochemistry, and behavior
May 1, 1989
M P Johnson, D E Nichols
26 citations
A behaviorally equipotent dose of the MDMA analogue MBDB (25 mg/kg) produced significant decreases in serotonin, its metabolite 5-HIAA, and serotonin uptake sites in rat cortex, similar to the nearly 60% reductions caused by MDMA (20 mg/kg) two weeks after treatment. However, MBDB appeared slightly less neurotoxic than MDMA. Unlike MDMA, MBDB did not cause a significant increase in dopamine levels three hours after a single injection. The findings suggest that dopamine release may play a role in MDMA's neurotoxicity.
Pharmacology, biochemistry, and behavior
May 1, 1995
R P Kesner, P Jackson-Smith, C Henry et al.
25 citations
Ibogaine, a naturally occurring alkaloid, reduces withdrawal symptoms from morphine but also impairs sensory-motor function, activity, and learning in rats. At doses of 20-60 mg/kg, rats showed slower response times and motor reflex impairments at 40-60 mg/kg. Locomotor and nonlocomotor activity, as well as emotionality, were reduced at 10-40 mg/kg, with near-inactivity at higher doses. Learning a spatial location task was also impaired, likely due to reduced activity and sensory detection. A single 40 mg/kg injection caused learning deficits 1 day after, but not 7 days after, without affecting sensory-motor function at those times. Thus, ibogaine produces acute sensory-motor and activity problems and long-term learning deficits without lasting sensory-motor changes.
Pharmacology, biochemistry, and behavior
April 1, 1983
R Santos, E A Carlini
25 citations
Rats deprived of REM sleep for three days showed a stronger serotonin syndrome and more head shakes than control rats when given serotonin precursors (L-5-hydroxytryptophan or L-tryptophan, with or without MAO inhibitors). However, REM deprivation did not change the rats' response to the serotonin agonists MeO-DMT (0.75-6.0 mg/kg) or quipazine (2.4-6.0 mg/kg), and reduced their response to lower doses of quipazine (0.3-1.25 mg/kg). The findings suggest that increased serotonin turnover during REM deprivation may enhance precursor effects, while reduced responsiveness to quipazine may reflect receptor hyposensitivity from intense activation.
Pharmacology, biochemistry, and behavior
January 1, 2016
Amir H Rezvani, Marty C Cauley, Susan Slade et al.
22 citations
The ibogaine derivative 18-methoxycoronaridine (18-MC), given orally, reduced nicotine and alcohol self-administration in rats. In female rats trained to self-administer nicotine, a single 40 mg/kg oral dose significantly decreased nicotine intake, particularly in animals with lower baseline consumption. In alcohol-preferring rats of both sexes, 18-MC dose-dependently reduced alcohol intake, with all tested doses (10, 20, 40 mg/kg) producing significant reductions. These results indicate that oral 18-MC is effective in curbing both alcohol and nicotine seeking, supporting its potential as a therapy for alcoholism and smoking addiction.
Pharmacology, biochemistry, and behavior
August 1, 2004
Nantaka Khorana, Manik R Pullagurla, Malgorzata Dukat et al.
21 citations
Two sulfur-containing phenylalkylamines, 4-MTA and 2C-T-7, gaining popularity on the illicit drug market, were tested in rats trained to discriminate the hallucinogen DOM, the stimulant cocaine, or the empathogen MDMA from a neutral substance. 4-MTA and its analog 4-MTMA substituted only for MDMA, whereas 2C-T-7 substituted only for DOM. These results indicate that 4-MTA and 4-MTMA act like MDMA, while 2C-T-7 behaves like a DOM-like hallucinogen, extending knowledge of structure-activity relationships and aligning with limited human reports.
Pharmacology, biochemistry, and behavior
April 1, 1996
H Sershen, A Hashim, A Lajtha
21 citations
Ibogaine, a compound with structural similarity to serotonin, blocks cocaine's effect on serotonin release in mouse striatal tissue, which in turn modulates dopamine release. In mice treated with ibogaine, cocaine no longer increased electrically evoked serotonin efflux, though dopamine efflux remained elevated. A kappa-opioid agonist reduced both dopamine and serotonin release, an effect blocked by ibogaine pretreatment. The kappa-opioid agonist also restored cocaine-induced serotonin release in ibogaine-treated tissue. These findings suggest ibogaine's antiaddictive properties involve blocking cocaine's serotonergic effects and altering kappa-opioid modulation of serotonin transmission.
Pharmacology, biochemistry, and behavior
December 1, 2023
Guilin Liu, Li Ma, Youge Qu et al.
16 citations
Arketamine, but not the psychedelic drugs DOI or lisuride, produced long-lasting prophylactic effects in mouse models of depression. Male mice pretreated with arketamine six days before an immune challenge (lipopolysaccharide, LPS) showed reduced body weight loss, less spleen enlargement, less immobility in a forced swim test, and higher levels of the synaptic protein PSD-95 in the prefrontal cortex compared to mice pretreated with DOI or lisuride. Similarly, arketamine given one day before seven days of chronic restraint stress prevented increased immobility, restored sucrose preference, and protected PSD-95 expression. DOI and lisuride did not show these protective effects.
Pharmacology, biochemistry, and behavior
February 1, 1998
S Helsley, R A Filipink, W D Bowen et al.
16 citations
Ibogaine, a hallucinogen with potential for treating addiction, produces its effects through interactions with multiple brain receptors. In rats trained to recognize ibogaine, ligands targeting sigma2 and opiate receptors partially reproduced ibogaine's effects, while sigma1-selective agents did not. Morphine and kappa-selective opioids failed to substitute for ibogaine, but mixed-action opiates like (-)-SKF 10,047 and nalorphine showed intermediate generalization. Naloxone partially blocked ibogaine's effects and fully blocked those of (-)-SKF 10,047 and nalorphine. Neither PCP nor MK-801 substituted for ibogaine, indicating NMDA receptors are not involved. The findings suggest that sigma2 and opiate receptors, but not NMDA receptors, contribute to ibogaine's discriminative stimulus.
Pharmacology, biochemistry, and behavior
January 1, 2001
J B Rangisetty, M L Bondarev, J Chang-Fong et al.
14 citations
Psychoactive phenylisopropylamines can produce different stimulus effects in animals, typified by hallucinogen DOM, stimulant amphetamine, and the less understood agent PMMA. In rats trained to discriminate PMMA from vehicle, the PMMA stimulus generalized to both optical isomers of MBDB and 3,4-DMA, with S(+)-MBDB (ED50=0.8 mg/kg) more potent than R(-)-MBDB (2.0 mg/kg) and S(+)-3,4-DMA (2.6 mg/kg) more potent than R(-)-3,4-DMA (3.9 mg/kg). These agents produce stimulus effects similar to PMMA. Both isomers of 3,4-DMA substituted for an MDMA stimulus but not for DOM or amphetamine stimuli. The evidence suggests PMMA, both isomers of MBDB and 3,4-DMA, and S(+)-MDMA produce common stimulus effects in rats, better defining the PMMA stimulus and structural requirements for this effect.
Pharmacology, biochemistry, and behavior
July 1, 1999
J C Winter, S Helsley, D Fiorella et al.
14 citations
Pretreatment with the monoamine reuptake inhibitors fluoxetine, fluvoxamine, and venlafaxine increased the discriminative stimulus effects of the hallucinogens LSD, (-)-DOM, and ibogaine in rats trained to recognize these drugs. For 5-MeO-DMT-trained rats, only fluoxetine enhanced drug-appropriate responding. The reuptake inhibitors alone sometimes produced intermediate responding, suggesting partial substitution. Further experiments with (-)-DOM showed that most combinations produced additive rather than truly potentiating effects. The findings extend earlier observations that fluoxetine augments LSD's effects to include other hallucinogens, though the mechanisms and differences between acute and chronic treatment remain unknown.
Pharmacology, biochemistry, and behavior
July 1, 1999
K K Szumlinski, I M Maisonneuve, S D Glick
14 citations
A single injection of ibogaine, given 19 hours before a cocaine challenge, more strongly amplifies cocaine-induced movement in rats that have a history of chronic cocaine use than in rats without prior cocaine exposure. The effect grows larger after a second ibogaine treatment but disappears within 24 hours when ibogaine is no longer given. Tolerance to cocaine's stimulant effects appeared in rats that received only cocaine without ibogaine. These results show that ibogaine heightens sensitivity to cocaine's psychomotor effects, and the size of this enhancement depends on the animal's past experience with both ibogaine and cocaine.
Pharmacology, biochemistry, and behavior
May 1, 2024
Li Ma, Akifumi Eguchi, Guilin Liu et al.
11 citations
Pretreatment with the antidepressant arketamine prevented stress-induced body weight loss, increased behavioral despair, decreased sucrose preference, and reduced synaptic protein expression in the prefrontal cortex of male mice exposed to chronic restraint stress. Gut microbiota analysis indicated that arketamine may restore stress-related changes in microbial abundance. Metabolomics identified four blood metabolites altered between stress-exposed and arketamine-pretreated mice. Network analysis linked synaptic proteins in the prefrontal cortex with specific gut microbes and blood metabolites. These findings suggest that the gut-brain axis, including microbial metabolites, may partly underlie the sustained prophylactic effects of arketamine.
Pharmacology, biochemistry, and behavior
February 1, 1998
H E Jones, H Li, R L Balster
11 citations
Ibogaine did not produce effects similar to phencyclidine (PCP) in rats or rhesus monkeys trained to discriminate PCP from saline or sham injection. In rats, ibogaine showed no substitution for PCP at doses from 5.6 to 17.6 mg/kg. In monkeys, ibogaine also failed to generalize to PCP at doses from 0.5 to 4.0 mg/kg. Lysergic acid diethylamide (LSD) only partially substituted for PCP in rats and produced little PCP-associated lever pressing in monkeys. These results indicate important behavioral differences between PCP and hallucinogens like LSD and ibogaine and do not support the idea that ibogaine's binding to the PCP site on NMDA receptors drives its acute effects.
Pharmacology, biochemistry, and behavior
January 1, 1983
P Cazala, A M Garrigues
11 citations
Injecting mice with drugs that affect dopamine, serotonin, or norepinephrine alters their approach and escape behaviors triggered by brain stimulation. Apomorphine, which mimics dopamine, slowed both approach and escape reactions, more so in BALB/c mice. Clonidine, which mimics norepinephrine, sped up approach only in BALB/c mice. 5-m-DMT, which mimics serotonin, slowed escape in DBA/2 mice only. These results suggest that dopamine regulates escape from midbrain stimulation, serotonin modulates escape from both brain areas, and norepinephrine influences the appetitive component of hypothalamic stimulation. Approach and escape reactions depend on separate neuronal populations.
Pharmacology, biochemistry, and behavior
September 1, 2011
J C Winter, D J Amorosi, Kenner C Rice et al.
10 citations
In mice genetically modified to express human CYP2D6 (Tg-CYP2D6) and wild-type mice, the psychedelic 5-MeO-DMT produced similar rates of learning a drug discrimination task. Bufotenine did not substitute for 5-MeO-DMT, while its lipid-soluble analog acetylbufotenine produced intermediate substitution. Combining harmaline with 5-MeO-DMT significantly increased drug-appropriate responding in both mouse types, indicating harmaline enhances 5-MeO-DMT's stimulus effects. Harmaline alone also produced significant 5-MeO-DMT-appropriate responding in Tg-CYP2D6 mice, suggesting metabolic interactions. No differences between wild-type and Tg-CYP2D6 mice were found in acquisition or responses to bufotenine and acetylbufotenine.
Pharmacology, biochemistry, and behavior
December 1, 1986
R Young, J A Rosecrans, R A Glennon
10 citations
In rats trained to distinguish the psychedelic compound 5-methoxy-N,N-dimethyltryptamine (5-OMe DMT) from saline, the serotonin antagonist cyproheptadine completely blocked the drug's effects at a low dose, while cinanserin and methergoline partially blocked them, and methysergide had little effect. At a higher dose of 5-OMe DMT, methysergide and methergoline partially blocked the drug's effects, but cyproheptadine and cinanserin did not. The authors advise caution when drawing conclusions from studies using these drugs until their in vivo effects and mechanisms are better understood.
Pharmacology, biochemistry, and behavior
September 1, 2024
Samantha L Penman, Nicole M Roeder, Jia Wang et al.
9 citations
Prenatal exposure to vaporized THC, the psychoactive component of cannabis, may lead to attention deficits and altered memory performance in adolescence. In a rodent study, pregnant rats inhaled THC daily from early pregnancy until birth. Their offspring, raised on either a standard or high-fat diet, were tested in early and late adolescence. Low-dose THC exposure reduced object exploration in memory and attention tests, indicating decreased attention. Female offspring showed even lower attention than males. Some learning pattern differences appeared in the high-dose group during early adolescence, but final memory performance was unaffected. This is the first study to examine vaporized THC's effects on adolescent memory and attention.
Pharmacology, biochemistry, and behavior
September 1, 1997
S Helsley, D Fiorella, R A Rabin et al.
9 citations
Ibogaine, at a potentially neurotoxic dose, did not impair rats' ability to learn or perform a maze task. In a study with 12 rats trained in an 8-arm radial maze, those given ibogaine showed similar learning and accuracy as controls but had lower response rates. When given before maze sessions, ibogaine dose-dependently slowed responding without reducing accuracy. When given after sessions, ibogaine-treated rats made fewer errors than controls. The authors conclude that ibogaine failed to produce any harmful effects on learning or task efficiency.
Pharmacology, biochemistry, and behavior
July 1, 2024
Deren Aykan, Mert Genc, Gunes Unal
8 citations
Combining environmental enrichment with ketamine produces a synergistic antidepressant effect in adult male Wistar rats. Environmental enrichment also reversed spatial memory deficits caused by ketamine in the Morris water maze. Enhanced neuronal activity was observed in the habenula of rats housed in an enriched environment alone after the probe trial, but not in enriched animals that also received ketamine. The findings suggest that sensory-motor stimulation can boost ketamine's antidepressant properties while reducing cognitive side effects, pointing to the potential of pairing pharmacological and environmental interventions for mood disorders.
Pharmacology, biochemistry, and behavior
March 1, 2025
Joel S Raymond, Alexander G Athanasopoulos, Connie J Badolato et al.
7 citations
Medications for substance use disorders are limited, especially for stimulants and cannabis, due to addiction's biological complexity, regulatory hurdles, and pharmaceutical industry disinterest. The opioid crisis has spurred urgent efforts to find new treatments. Several neurobiological systems newly implicated in drug reward offer novel medication targets. This review covers ongoing clinical trials and authors' research on psychedelics targeting serotonin 2A receptors, glucagon-like peptide 1 receptor agonists, cannabidiol, dynorphin/kappa opioid receptor, orexin/hypocretin, and oxytocin receptor systems, plus agonist therapies for stimulant use disorders. These innovations suggest an improved therapeutic landscape is near.
Pharmacology, biochemistry, and behavior
September 1, 2009
Vikas Duvvuri, Victoria B Risbrough, Walter H Kaye et al.
7 citations
A translational model of anorexia nervosa (AN) was tested using a hyponeophagia assay in mice, where food-deprived animals showed increased latency to begin feeding in a novel, anxiety-provoking environment. The non-selective serotonin agonist 5-MeODMT potentiated feeding inhibition beyond that caused by the environment alone, indicating a drug-by-environment interaction. Blocking the 5-HT(1A) receptor with WAY100635 reversed this effect, supporting a necessary role for 5-HT(1A) receptor activation in feeding inhibition. The findings suggest a mechanistic link between elevated 5-HT(1A) receptor activity and restricting-type AN, with implications for the interplay between anxiety and appetite suppression.